Journal of Experimental Psychology:Animal Behavior Processes1980, Vol. 6, No. 1, 49-64

Aftereffects of Lithium-Conditioned Stimulion Consummatory Behavior

in the Presence or Absence of the DrugMichael Domjan, Douglas J. Gillan, and Gail A. Gemberling

University of Texas at Austin

Drinking is increased by prior exposure to lithium-conditioned stimuli. Ex-periment 1 showed that this phenomenon is not an artifact of testing subjectswith a novel, palatable drinking fluid and also showed that lithium-condi-tioned olfactory stimuli produce a biphasic change in drinking, with drinkingsuppressed at the start of exposure to the conditioned stimulus (CS) andenhanced a long time after CS onset or exposure. Experiment 2 showed thatthe increased drinking aftereffect of lithium-conditioned stimuli is not a re-sult of the instrumental reinforcement of the drinking response by the sched-uling of water access following drug injections during conditioning, andExperiments 3, 4, and 5 showed that the increased drinking effect occurseven if subjects are injected with lithium prior to the test session. The resultsof Experiments 3 and 5 also showed that lithium administration and expo-sure to lithium-conditioned stimuli have independent and opposite aftereffects:Lithium disrupts drinking, whereas prior exposure to lithium-conditionedstimuli increases consumption. The relevance of conditioned opponent andcompensatory processes to the findings is discussed.

Although most Pavlovian conditioning ex-periments have been primarily concernedwith the conditioned responses that occur inthe presence of the conditioned stimulus,there is also evidence that conditioned stim-uli have important effects following theirpresentation. Pavlov (1927) found, for ex-ample, that the response to an excitatoryconditioned stimulus (CS+) was potentiatedfollowing exposure to an inhibitory condi-tioned stimulus (CS-). In more recent ex-periments, presentation of an excitatory con-ditioned stimulus has been found to decreaseresponding elicited by subsequent presenta-tions of the same CS (Pfautz & Wagner,1976). Exposure to an excitatory condi-

The research was supported by Grants BNS77-01552 from the National Science Foundation andMH 30788-01 from the Public Health Service. Weare grateful to Michael Hanlon for helping withdata collection and analysis.

Requests for reprints should be sent to MichaelDomjan, Department of Psychology, Mezes 330,University of Texas, Austin, Texas 78712.

tioned stimulus also has been observed todecrease responding subsequently elicited bythe unconditioned stimulus (US; e.g.,Kimble & Ost, 1961).

The above examples involved the after-effects of conditioned stimuli on responseselicited by CSs and USs that served in theearlier conditioning phase of the experi-ments. In contrast, Domjan and Gillan(1977) recently investigated the aftereffectsof a CS on responses to stimuli that were notinvolved in initial conditioning. In their ex-periments, gustatory and exteroceptive cueswere first conditioned by pairing these stim-uli with the administration of the drug lith-ium chloride. The aftereffects of these con-ditioned stimuli were then evaluated by ob-serving how exposure to the CSs influencedthe subjects' subsequent intake of a novel,palatable taste solution or of water. The lith-ium-conditioned stimuli elicited above-nor-mal levels of consumption in both types oftests. This increased drinking was not merelya result of the conditioned aversiveness of

Copyright 1980 by the American Psychological Association, Inc. 0097-7403/80/0601-0049300.75

49

50 M. DOMJAN, D. GILLAN, AND G. GEMBERLING

the lithium-paired cues (Domjan & Gillan,1977). However, conditioning clearly wasinvolved because the enhanced consumptionwas not observed after exposure to stimulipaired with the absence of lithium and wasattenuated by extinction (Domjan & Gillan,1977).

The increased drinking phenomenon isnoteworthy not only because it representsan aftereffect of CSs on responses to stimulinot involved in the earlier conditioning phasebut also because of the nature of the behaviorobserved. Drinking is typically suppressed inthe presence of lithium-conditioned stimuli(for reviews see Barker, Best, & Domjan,1977; Milgram, Krames, & Alloway, 1977).Drinking is also disrupted by lithium treat-ment (e.g., Domjan, 1977; Kutscher &Wright, 1977). Thus, the increased drinkingaftereffect of lithium-conditioned stimuli isopposite the behavior observed during theCS and US in this situation.

Previous research has left many questionsunanswered concerning the enhanced drink-ing effect. It may be, for example, that thecritical variable for observation of the phe-nomenon is not testing subjects after ex-posure to lithium-conditioned stimuli butrather testing them with a palatable drinkingfluid. Studies showing suppressed drinkingin the presence of lithium-conditioned cueshave usually involved giving subjects a con-ditioned aversive substance to drink. In con-trast, our experiments showing increaseddrinking have involved giving subjects ac-cess to palatable drinking fluids (Domjan &Gillan, 1977). Thus, the difference in out-comes may reflect differences in the testsolutions used rather than differences in thetime of testing.

In addition to clarifying the test proce-dures necessary for the enhanced drinkingeffect, further research is also required toidentify what processes are responsbile forthe phenomenon. Because the reaction ob-served is opposite the direct effects of thedrug on consumption, the phenomenon mayreflect a compensatory response conditionedby the drug administrations (cf. Siegel,1975, 1977b). Alternatively, the enhancedconsumption may be an opponent aftereffect

of the suppression of drinking which occursin the presence of lithium-conditioned stim-uli (cf. Solomon & Corbit, 1974). It is alsopossible that during the conditioning phase,subjects learn that drinking alleviates themalaise produced by lithium treatment (cf.Smith, Balagura, & Lubran, 1970), andthe increased drinking may be an anticipa-tory antidotal response elicited by the ex-pectancy of lithium (Mineka, Seligman, Het-rick, & Zuelzer, 1972). Finally, the increaseddrinking may occur because the lithium-paired flavor is not followed by drug treat-ment for the first time during the test session.This unexpected absence of drug treatmentmay stimulate increased drinking uncondi-tionally or by conditioning inhibitory prop-erties to the ingested test fluid (e.g., Best,1975).

The present experiments were designed toexplore the boundary conditions of the in-creased consumption effect and to help iden-tify the mechanisms responsible for the phe-nomenon. Experiment 1 was conducted toreplicate the enhanced drinking effect witholfactory conditioned stimuli and to deter-mine whether subjects increase their drink-ing shortly after CS exposure and suppresstheir drinking in the presence of the drug-conditioned odors even if the same drinkingsolution is used during both types of testsessions. Experiment 2 investigated whetherthe phenomenon occurs even if the condition-ing procedure is modified to prevent the as-sociation of drinking with recovery fromlithium malaise, and Experiments 3-5 wereperformed to determine whether the in-creased drinking occurs even if subjects aregiven a drug injection after exposure to thelithium-conditioned stimulus during the testsession.

Experiment 1

As was noted earlier, most studies of theeffects of the presence of lithium-conditionedstimuli on drinking have involved test pro-cedures in which lithium-conditioned tastecues were presented contingent on the drink-ing response. In contrast, the increaseddrinking aftereffect of lithium-conditionedstimuli has been observed with palatable, and

AFTEREFFECTS OF LITHIUM-CONDITIONED STIMULI 51

usually novel, solutions presented contingenton drinking. Experiment 1 was designed tomeasure drinking during and after exposureto drug-conditioned stimuli, using the samenovel palatable drinking fluid in all cases.The drug-conditioned stimulus was the odorof Mentholatum. After conditioning, a drink-ing test with a novel 3% solution of vanillawas conducted either in the presence of theodor or 5 or 25 min following odor exposurefor independent groups. Similar test sessionswere conducted for control groups that previ-ously received unpaired exposure to Mentho-latum and lithium and subjects that previ-ously received only exposure to the odorstimulus.

Method

Sixty male Sprague-Dawley rats, 200-250 g atthe start of the experiment, were individuallyhoused with 30-min daily access to tap water andcontinuous access to Wayne Lab Blox. After adap-tation to the deprivation schedule, the subjects weredistributed among three groups for conditioning.Group CS+ (n ~ 26) received the odor of Men-tholatum paired with an ip injection of 2.25 mEq/kg.15 M lithium chloride. Group CS— (n = 17) re-ceived the odor of Mentholatum paired with an ipinjection of 2.25 mEq/kg physiological saline andreceived a 2.25 mEq/kg lithium injection 24 hrlater. Finally, Group Con (n = 17) was treatedthe same way as Group CS— but never receivedthe lithium injections. Odor-exposure trials wereconducted at 3-6-day intervals, and on treatmentdays the daily 30-min access to water was given1.5-4.5 hr after the experimental treatment.

The odor was presented by placing the subjectsin a 10,300-cm" 29-cm-high plastic pail. The insidesurface of the tightly fitting lid of each pail wassmeared with approximately 14 g of Mentholatum.For each odor exposure, subjects were placed inthe odorized pails for 30 min. Ten minutes afterplacement in the odor chambers, subjects wereremoved just long enough to receive their lithiumor saline injection. Six odor chambers were usedsimultaneously in an experimental room separatedfrom the animal colony room by a hallway. The sixsubjects in each squad were placed in the odorchambers at 30-sec intervals, and the compositionof the squads as well as the position of each sub-ject within a squad was varied across trials. A totalof 10 odor-exposure trials were conducted for eachsubject.

The test session was conducted 3-4 days afterthe 10th trial. The effects of three different testprocedures were assessed. Subjects in test condi-tion Simult (simultaneous) were placed in the odor-exposure chambers for 30 min as usual. However,

this time a drinking spout providing access to a3% (v/v) solution of vanilla extract (Piedmont)was inserted into the odor chamber through ahole 7.6 cm from the floor. (When not in use, thishole was covered by a metal plate.) Subjects intest condition 5' Post were placed in the odor cham-ber for 30 min as usual and received access to the3% vanilla solution for 120 min in their homecages starting 5 min after the end of the odorexposure. Finally, subjects in test condition 25'Post were treated the same way as those that re-ceived test procedure 5' Post except that their 120-min access to the vanilla solution began 25 minafter the end of their odor exposure. Subjects in allthree test conditions received a 2.25 mEq/kg in-jection of .15 M NaCl 10 min after being placedin the odor chambers on the test day. The vanillawas provided in 50-ml graduated centrifuge tubesfitted with black rubber stoppers and stainlesssteel drinking spouts. Intakes during the vanillatest were recorded at 5-min intervals in the odorchambers and at 10-min intervals in the homecages.

Of the 26 subjects in Group CS+, 8 receivedtest procedure Simult, 9 received test procedure5' Post, and 9 received test procedure 25' Post.Five of the subjects in each of Groups CS— andCon received test procedure Simult, 6 subjects ineach of these groups received test procedure 5'Post, and 6 subjects in each of these groups re-ceived test procedure 25' Post. Thus, the experi-mental design was a 3 X 3 factorial, with the re-sults of three conditioning procedures (CS+, CS—,and Con) assessed with three test procedures (Si-mult, 5' Post, and 25'Post).

Results

The cumulative intake of subjects givenaccess to the vanilla solution for 30 min inthe presence of the odor of Mentholatum(Simult) and of subjects tested for 120min starting 5 min (5' Post) and 25 min(25' Post) after the odor exposure is pre-sented in Figure 1. Subjects for which theMentholatum odor had been paired withlithium (Group CS+) drank much lessvanilla in the presence of this odor (Simult)than the subjects for which Mentholatum andlithium had been unpaired (Groups CS —)and the subjects that had never been injectedwith lithium (Group Con). In contrast tothis suppression of intake evident in the pres-ence of the lithium-conditioned odor, ex-posure to this odor 5 min or 25 min beforethe vanilla test resulted in increased con-sumption. Group CS+ drank more vanillathan either Group CS— or Group Con after

52 M. DOMJAN, D. GILLAN, AND G. GEMBERLING

3O

25-

QkJ

20-

U

15

1O

Con

Simult

/**/

30 0

5' Post

30 60 90 120 0MINUTES

25' Post

30 60 90 120

Figure 1. Mean cumulative intake of a novel vanilla solution in Experiment 1. (The odor ofMentholatum was previously paired with lithium for Group CS+, presented 24 hr before lithiumtreatments for Group CS— and presented without any lithium treatments for Group Con. Thevanilla test was conducted in the presence of the Mentholatum odor for some subjects [Simult]and was started 5 min and 25 min after exposure to the Mentholatum odor for other animals[5' Post and 25' Post, respectively].)

exposure to Mentholatum. However, thisincreased drinking was not clearly evidentuntil the latter portions of the vanilla test.

The vanilla test lasted much longer forsubjects given access to this solution afterexposure to the odor of Mentholatum (5'Post and 25' Post) than for subjects testedsimultaneously with the odor exposure. How-ever, all subjects received access to the va-nilla flavor for at least 30 min. The totalamount of vanilla each group drank duringthis 30-min period was first evaluated with a3 (Conditioning Treatments) X 3 (Odor-to-Test Intervals) analysis of variance. Thisanalysis indicated that.the main effect of con-ditioning treatments was not significant(F < 1.0). However, the main effect of theodor-to-test interval, F(2, 51) = 18.52, /> <.01, and the interaction between conditioningtreatments and the test interval, F(4, 51) =8.45, p < .01, were both significant. One-way analyses of variance were then con-

ducted to determine the source of the inter-action between the conditioning . and testinterval variables. These analyses indicatedthat there were no significant differencesamong the conditioning groups given accessto vanilla starting 5 min and 25 min after ex-posure to the Mentholatum odor, Fs(2,20) =2.37 and 1.42, ps > .10, respectively. How-ever, the groups given access to vanilladuring the Mentholatum odor differed sig-nificantly, F(2, 15) = 10.67, p < .01, andsubsequent comparisons with the Newman-Keuls test (p < .05) showed that GroupCS+ drank significantly less vanilla duringthe Mentholatum odor than either GroupCS— or Group Con, which did not differfrom each other.

Further comparisons of the amount ofvanilla each group drank during the first 30min indicated that the intakes of GroupsCS— and Con were not influenced by theinterval between exposure to the Mentho-

AFTEREFFECTS OF LITHIUM-CONDITIONED STIMULI S3

latum odor and the beginning of the vanillatest (Fs< 1.0). However, the odor-to-testinterval significantly affected the intakes ofGroup CS+, F(2, 23) = 34.94, p < .01.Comparisons with the Newman-Keuls test(/> < .05) showed that subjects in GroupCS+ that were given access to vanilla dur-ing the Mentholatum odor drank signifi-cantly less in 30 min than subjects that weretested starting 5 min and 25 min after odorexposure, and these latter subjects did notdiffer significantly from one another.

Although differences in vanilla intake asa function of conditioning were not evidentduring the first 30 min for subjects testedstarting 5 min and 25 min after exposure toMentholatum, such group differences emergedlater during the vanilla test. With both odor-to-test intervals, subjects for which Mentho-latum had been paired with lithium (GroupCS+) drank more during the entire 120-mintest session than subjects for which the odorand the drug had been unpaired (GroupCS—) or subjects that had never been in-jected with the drug (Group Con; see Fig-ure 1). The total amount of vanilla con-sumed in the 5' Post and 25' Post test pro-cedures was evaluated with separate one-wayanalyses of variance. These analyses con-firmed the existence of group differences,Fs(2, 18) =6.98 and 5.78, ps < .05, re-spectively. Subsequent comparisons with theNewman-Keuls test (p < .05) indicated thatGroup CS+ drank significantly more vanillathan either Group CS— or Group Con,which did not differ from each other, in boththe 5' Post and 25' Post test conditions.

Discussion

The results of Experiment 1 replicate andextend several earlier observations. The be-havior of subjects given the drinking testin the presence of Mentholatum (test pro-cedure Simult) confirms that the consum-matory behavior of subjects is suppressed inthe presence of lithium-conditioned olfactorystimuli (e.g., Domjan, 1973). In contrastto the suppression of drinking which wasevident in the presence of the lithium-condi-tioned cues, subjects in Group CS+ drank

more than the comparison Groups CS— andCon when a longer drinking test was con-ducted and the test session was started afterodor exposure. This latter outcome indicatesthat the enhanced-drinking aftereffect of lith-ium-conditioned stimuli is not limited to thegustatory and spatial conditioned stimulithat were used in previous demonstrations(Domjan & Gillan, 1977).

Since the same novel flavored solutionwas used to test drinking responses duringand after exposure to the lithium-conditionedstimuli, the difference in outcomes observedcannot be attributed to differences in lick-contingent stimulation. However, it is notclear from the present experiment that sub-jects have to be tested in the absence of thedrug-conditioned stimuli to manifest the in-creased drinking effect. It may be that in-creased drinking would be evident towardthe end of a 120-min vanilla test whether ornot the drug-conditioned odor is presentthroughout the test period. Nevertheless, thepresent findings clearly demonstrate thatlithium-conditioned stimuli have a biphasiceffect on drinking. Ingestion is suppressed atthe start of exposure to the drug-conditionedstimuli, in a manner similar to the directeffects of the drug on drinking (e.g., Dom-jan, 1977). In contrast, ingestion is in-creased if subjects are tested a longer pe-riod following the presentation of the drug-conditioned cues, in a manner opposite theeffects of lithium on drinking.

The biphasic character of the drinkingresponse to lithium-conditioned stimuli isconsonant with the opponent-process theoryof motivation (Solomon, 1977; Solomon &Corbit, 1974). This theory predicts that as aresult of the pairing of a stimulus with theonset of drug effects, as was done in thepresent study, the stimulus will become con-ditioned to elicit the primary or a drug pro-cess. This will in turn evoke a "slave" op-ponent or b process whose behavioral mani-festations are assumed to be opposite thosethat accompany the primary process. Thesuppression of drinking observed in the pres-ence of the lithium-conditioned odor cuesmay be interpreted as indicative of the con-ditioned primary drug process, and the in-

54 M. DOMJAN, D. GILLAN, AND G. GEMBERLING

creased drinking observed later may be in-terpreted as indicative of the opponent bprocess.

Experiment 2

With the conditioning procedures used inExperiment 1 and in the studies by Domjanand Gillan (1977), subjects received theirdaily access to water after being injectedwith lithium. This postinjection drinkingmay have facilitated excretion of the drug(cf. Smith et al., 1970) and thereby allevi-ated lithium malaise. Alternatively, the post-injection drinking may have occurred whenlithium effects were abating. In either case,drinking would have been reinforced by areduction in illness. Since this reinforcementoccurred only following exposure to theCS + , the animals may have learned to in-crease drinking after the CS+ because of theinstrumental contingency between the drink-ing response and reduction in sickness.

The conditioning procedure used in Ex-periment 2 was designed to reduce the pos-sibility of learning that drinking is corre-lated with a reduction in lithium malaise.Subjects were given their daily 30-min ac-cess to water 1.5-2.5 hr before each condi-tioning trial and were not given access towater again until the next day. Thus, theywere deprived of water for 21-22 hr aftereach conditioning trial. Lithium malaise ap-pears to last little more than 2 hr. Fluid con-sumption (e.g., Domjan, 1977) as well asplasma corticosterone levels (Weinberg,Smotherman, & Levine, 1978) returns tonormal within 2 hr of lithium treatment.Therefore, it is likely that subjects hadtotally recovered from lithium malaise by thetime they received access to water aftereach conditioning trial.

Because most of our previous studies in-volved taste solutions as drug-paired stimuli(Domjan & Gillan, 1977, Experiments 1-4;Domjan, Gemberling, & Gillan, Note 1),taste cues were also used in Experiment 2.The method was modeled after the proce-dures used by Domjan and Gillan (1977).

Method

Six male and six female SO-60-day-old Sprague-Dawley rats were individually housed in hangingwire mesh cages. All subjects had a cannula im-planted in the cheek to permit the infusion oftaste solutions into the oral cavity. During etheranesthesia, a section of Clay-Adams polyethylenetubing (PE-205) was passed under the skin of theneck, with one end exiting at the back of the neckand the other entering the oral cavity near theright molar teeth. The two ends were flared andheld in place by polyethylene washers and by awire suture attached to the oral end and affixedto subcutaneous tissue in the cheek. The subjectswere maintained with continuous access to PurinaRat Chow and water for 2-3 wk before the startof the experiment. Access to water was then givenonly from 8:30 a.m. to 9:00 a.m. each day. Thewater was always mixed with Terramycin to helpcontrol infections and respiratory disease. All ex-perimental sessions were conducted 1.5-2.S hr aftersubjects received their daily 30-min access to wa-ter, and no other fluids were presented until thenext day.

Six infusion-adaptation sessions were administeredon successive days starting on the ninth day of thewater deprivation schedule. Within 2 min beforeeach session, each subject's cannula was rinsedwith 2-3 ml of tap water. The subjects were thenindividually placed in a wire mesh cage whosewalls had been extended to prevent the rats fromjumping out. The cannulas were connected withflexible Tygon Formula B44-3 tubing to a SO-mlsyringe in a Harvard Model 941 infusion pump,and tap water was infused into the oral cavity for5 min at a rate of 1.2 ml/min. Subjects were wipeddry with a paper towel after each infusion experi-ence to remove any unswallowed fluid that mayhave gotten on their fur.

Following the adaptation sessions, subjects re-ceived differential flavor-aversion conditioning.The oral infusion of one solution (the CS-f) wasfollowed .5-1.5 min later by an ip injection of 1.5mEq/kg .15 M lithium chloride, and the oral in-fusion of a different taste (the CS—) was followedby a comparable injection of sodium chloride. Each'infusion lasted 5 min and was administered at arate of 1.2 ml/min within 2 min after the cannulahad been rinsed with 2-3 ml of water. Three CS+and 3 CS— conditioning trials were administeredin an irregular order (H 1 h) with an inter-trial interval of 2 days. For half of the subjects, a2% (v/v) solution of cider vinegar (4.5% acidity)served as the CS+ flavor, and a \% (w/v) solu-tion of sodium chloride served as the CS— flavor;the remaining subjects received the opposite flavorassignments. Because subjects were always givenaccess to water only before the conditioning trialon conditioning days, they were deprived of waterfor 21-22 hr after each conditioning episode.

Two days after the last conditioning trial, sixsubjects (three for which the CS+ was vinegar

AFTEREFFECTS OF LITHIUM-CONDITIONED STIMULI 55

and three for which the CS+ was sodium) re-ceived a 5-min oral infusion of the CS+ flavor,immediately followed by a 1.5 mEq/kg injection ofphysiological saline. Fifteen minutes later, the sub-jects were given a 120-min one-bottle drinkingtest with a 3% (v/v) solution of vanilla extractin the home cages. The remaining six subjectswere treated the same way except that they re-ceived a 5-min oral infusion of tap water insteadof the CS+ solution before the vanilla test. Similartreatments were administered 2 days later exceptthat subjects that had received an oral infusionof the CS+ before the first vanilla test were nowinfused with water and those that had been in-fused with water before the first test were in-fused with the CS+ solution before the secondsession. In contrast to the adaptation and condition-ing trials, the vanilla tests were conducted beforesubjects received access to water for 30 min thatday.

Starting 2 days after the second vanilla test,subjects received a 30-min one-bottle test with theCS+ solution and a similar test with the CS—.These tests were conducted in a counterbalancedorder on successive days. The daily 30-min accessto water was provided after each of these testsessions.

One of the subjects for which vinegar served asthe CS+ died before the end of the experiment,and its data were therefore discarded.

Results and Discussion

The test sessions conducted at the end ofthe experiment with the CS+ and CS —solutions confirmed that the subjects hadlearned a discriminative flavor aversion.The mean test consumption of the CS+ andCS— solutions was 2.3 ml and 17.2 ml, re-spectively, and each subject drank more ofthe CS— than of the CS+ solution.

The cumulative amount of vanilla eachgroup drank following infusion exposure tothe CS+ or tap water is shown in Figure 2.As was the case in previous experiments(e.g., Domjan & Gillan, 1977), subjectsdrank more vanilla following presentation ofthe CS+ than following presentation of wa-ter. A t test cofnputed on the total vanillaconsumption during the two tests showedthat the difference was statistically signifi-cant, f(9)= 3.22, p < .01.

The present findings confirm that exposureto a lithium-conditioned stimulus increasessubsequent drinking in comparison with theeffects of the oral infusion of water. How-

25

cryin

15

10

CS+

0 30 60 90 120MINUTES

Figure 2, Mean cumulative vanilla consumptionduring a test session started 15 min after infusionexposure to the CS+ flavor (CS+) or to tap water(W) in Experiment 2. (During the earlier condi-tioning phase, access to fluids was always givenfollowing recovery from lithium malaise.)

ever, in contrast to previous experiments,subjects in the present study did not havespecific opportunity to learn that drinkingalleviates the malaise induced by lithium in-jection, or to experience the fortuitous pair-ing of drinking with the abatement of sick-ness during the experimental regimen. Eachlithium injection was followed by 21-22 hrof fluid deprivation. Since lithium sicknesspersists for about 2 hr (Domjan, 1977;Weinberg et al., 1978), it is unlikely thatwater consumption 21-22 hr after lithiumtreatment served to alleviate the drug-in-duced distress. Therefore, the enhanceddrinking observed after exposure to a sig-nal for lithium cannot be attributed to ex-perimentally induced learning that fluid in-take helps to reduce aversive aspects of thedrug.

Although the procedures of Experiment 2precluded the association of drinking withrecovery from lithium malaise, the nonex-perimental experiences of the subjects mayhave allowed for the association of drinkingwith recovery from other types of discom-fort, such as the ether anesthesia and thirst.Such factors are difficult, if not impossible, tocontrol.

56 M. DOMJAN, D. GILLAN, AND G. GEMBERLING

Experiment 3

The increased drinking effects reported inExperiments 1 and 2 as well as by Domjanand Gillan (1977) were observed after sub-jects were exposed to a lithium-conditionedstimulus without drug treatment. Further-more, the test session was the first timethat the lithium CS+ was not followedby a drug injection. Therefore, the in-creased drinking may have occurred as anunconditioned response to this unexpectedabsence of the drug. Perhaps the omissionof the drug increased the arousal of the sub-jects, and this in turn increased the rate oftheir predominant response. The predomi-nant response was probably drinking be-cause the subjects were water deprived andhad a palatable drinking fluid available. An-other possibilitiy is that the unexpected ab-sence of the drug conditioned inhibitoryproperties to the test flavor, and these prop-erties were responsible for the increaseddrinking observed (e.g., Best, 1975). Ex-periment 3 was conducted in part to evaluatethe importance of violations of drug expec-tancy for the increased drinking effect.

Subjects received differential condition-ing with .75 mEq/kg injections of lithiumfollowing each CS+ trial and control in-jections following each CS— trial. Afterthis preliminary phase, one group receiveda drinking test preceded by exposure to theCS+ and a control injection. For this group,the lithium injection was unexpectedlyomitted following exposure to CS+, as ithad been in all of our previous experiments.For a second group, the drinking test waspreceded by exposure to the CS+ and a .75mEq/kg lithium injection administered asduring initial conditioning. Thus, these sub-jects did not experience anything unexpectedbefore their drinking test session. A thirdgroup was also exposed to the CS+ but re-ceived a 1.5 mEq/kg lithium injection afterthis exposure rather than a .75 mEq/kg in-jection. Thus, these subjects received anunexpectedly large lithium dose before theirdrinking test. Because lithium suppressesconsumption in a dose-related manner (e.g.,Domjan, 1977), comparison groups weregiven the same lithium treatments before

the drinking test as the experimental groupsjust described.

If the increased drinking after exposure tothe CS+ is a result of the unexpected omis-sion of drug treatment, then only subjectsnot given lithium before the drinking testshould show the increased drinking effect.In contrast, if unexpected events generallystimulate increased consumption, then greaterintakes should be evident both with an un-expected decrease in lithium dose and withan unexpected increase in drug dose. Fi-nally, if a violation in the expectancy of lith-ium treatment is not necessary for the en-hanced drinking effect, then subjects shouldevidence increased intakes after exposure tothe CS+ regardless of whether the drugdose is increased, decreased, or not changedfrom the earlier conditioning phase.

In addition to evaluating the importance ofviolations of expectancy for the enhanceddrinking effect, Experiment 3 was also ex-pected to provide evidence relevant to in-terpretations of the phenomenon in terms ofconditioned compensatory response (Siegel,1975, 1977b) and conditioned opponent-process (Solomon, 1977) concepts. Accord-ing to both of these interpretations, the en-hanced drinking effect would be expected tosubtract from, but not otherwise interactwith, the suppressive effects of lithium ondrinking. That is to say, one would expectexposure to lithium-conditioned stimuli toenhance ingestion to the same degree rela-tive to control groups regardless of the pres-ence or absence of different degrees of drugtreatment on the test day.

Method

Sixty-four male SO-60-day-old Sprague-Dawleyrats were used in procedures identical to those ofExperiment 2 in all unspecified aspects. After re-covery from the cannula operation and adjust-ment to a daily 23.5-hr water deprivation schedule,each subject received four infusion-adaptation ses-sions conducted on alternate days. Subjects thenreceived three CS-f- and three CS— differentialconditioning trials in an irregular order(-1 1 h) , with an intertrial interval of 1-2days. Each CS+ trial ended with a .75 mEq/kginjection of .15 M lithium chloride, whereas eachCS— trial ended with a comparable injection ofphysiological saline. For 33 subjects a 2% vinegar

AFTEREFFECTS OF LITHIUM-CONDITIONED STIMULI 57

25

S20

15

1O

OmgqLi<No)

CS+.

O 30 6O 90 1200 30 60 9O 12OO 30 60 90 120

MINUTESFigure 3. Mean cumulative vanilla consumption in Experiment 3 during a test session started 15min after infusion exposure to the CS+ and CS— flavors and an injection of physiologicalsaline (0 mEq Li), .75 mEq/kg lithium or 1.5 mEq/kg lithium. (Subjects previously had theCS+ flavor paired with .75 mEq/kg lithium.)

solution served as the CS+, and a 1% sodiumchloride solution served as the CS—; for the re-maining subjects these flavor assignments werereversed.

Three to four days after the last conditioningtrial, each subject received a 120-min drinkingtest with a 3% vanilla solution. For Group NaCS+(» = 11, six with vinegar as CS+) the vanillatest occurred 15 min after the end of a 5-min in-fusion exposure to the CS+ solution, which wasimmediately followed by a .75 mEq injection ofphysiological saline. Group NaCS— (»= 11, sixwith vinegar as CS-t-) was treated as GroupNaCS+ except for being exposed to the CS—flavor 15 min before the vanilla test. Group .75CS+(w = ll, six with vinegar as CS+) received ex-posure to the CS+ solution followed by a .75mEq/kg injection of lithium 15 min before thevanilla test, whereas Group ,75CS— (n= l l , fivewith vinegar as CS+) was exposed to the CS—solution and injected with .75 mEq/kg of lithiumbefore the test session. Groups 1.5CS+ and 1.5CS—(ns = 10, five with vinegar as CS+) were treatedas Groups .75CS+ and .75CS—, respectively, ex-cept for being injected with 1.5 mEq/kg lithiuminstead of .75 mEq/kg lithium after the exposuresto the CS+ and CS— stimuli that preceded thevanilla test.

The decision to expose the control groups to theCS— flavor before the vanilla tests rather than towater infusion as in Experiment 2 was justified onthe basis of earlier research which had shown thatexposure to a CS— flavor and exposure to waterinfusion have the same effects on vanilla consump-tion in the absence of lithium treatment (Domjan &Gillan, 1977, Experiment 1). Additional evidence

for the appropriateness of CS— infusion for thecontrol groups is described in Experiment 4 of thepresent report.

Results

The amount of fluid each group drankcumulated over successive 10-min periods ofthe vanilla test is shown in Figure 3. Sub-jects tested 15 min after exposure to theCS+ flavor drank more than those that wereexposed to the CS— flavor before the testsession. This elevated consumption stimu-lated by exposure to the CS+ occurred re-gardless of the type of injection subjects re-ceived after the CS presentation. However,for subjects tested after a l.S mEq/kg lith-ium injection, the increased drinking effectwas not evident during the first few observa-tion intervals. Furthermore, drinking wasgenerally inversely related to the dose oflithium administered before the test session.Subjects given higher doses tended to drinkless.

The total vanilla consumption of each ofthe six groups was evaluated with a 3 X 2analysis of variance involving the three drugdoses and the two CSs that preceded the testsession. This analysis revealed a significanteffect of dose, F(2, 58) = 11.66, p < .01,

58 M. DOMJAN, D. GILLAN, AND G. GEMBERLING

and a significant effect of CS, F(l, 58) =18.17, p < .01. However, the interaction be-tween these two variables was not significant,F(2, 58) < 1.0.

Discussion

The present findings indicate that there isa dose-related decrement in drinking pro-duced by lithium treatment before the testsession. This outcome confirms previous ob-servations of the suppression of drinkingproduced by the administration of lithiumchloride (e.g., Domjan, 1977; Kutscher &Wright, 1977).

Despite the disruption of drinking causedby lithium treatment, exposure to the CS+flavor before the test session resulted in thedrinking of more fluid than similar exposureto the CS— flavor. Furthermore, this en-hanced drinking effect was independent ofthe dose of lithium administered prior to thetest session. This outcome indicates that theenhanced drinking effect does not requirethe unexpected absence of drug treatmentfollowing exposure to the CS+ on the testday. Therefore, it is unlikely that either thearousal resulting from violations of drugexpectancy or the conditioning of inhibitoryproperties to the ingested fluid is responsiblefor the aftereffects of lithium-conditionedstimuli on drinking.

The fact that exposure to the lithium-con-ditioned flavors subtracted from, but did nototherwise interact with, the effects of lithiumon drinking is consistent with interpretationsof the enhanced drinking effect in terms ofconditioned compensatory response (Siegel,1975, 1977b) and conditioned opponent-process (Solomon, 1977) concepts. Both ofthese mechanisms are assumed to detractfrom the primary effects of the drug usedin conditioning. Thus, these interpretationspredict that subjects previously exposed tothe CS+ will drink more than subjects previ-ously exposed to the CS —, even if lithium isadministered before the test session.

Experiment 4

Exposure to a lithium-conditioned CS +resulted in more drinking in Experiment 3

than similar exposure to a CS— whether ornot subjects received the drug in conjunc-tion with these stimulus presentations beforethe drinking test. The greater test consump-tion by lithium-injected subjects followingexposure to the CS+ compared with theCS— may have occurred because exposureto the CS+ flavor stimulated more drinkingthan what would have occurred otherwise.Another possibility is that exposure to theCS— flavor stimulated less drinking in thelithium-injected rats than what would haveoccurred otherwise. Experiment 4 was con-ducted to evaluate these alternatives. In ad-dition to testing lithium-injected subjectsafter exposure to the CS+ and CS —, somedrug-treated animals were also tested follow-ing infusion exposure to tap water or nofluids to determine baseline levels of drugeffectiveness.

Method

Fifty-eight male 50-60-day-old Sprague-Dawleyrats were used in procedures identical to those ofExperiment 2 in all unspecified respects. After re-covery from the cannula operation and adjustmentto a 23.5-hr daily deprivation schedule, subjects re-ceived four infusion-adaptation sessions conductedon successive days. Three CS+ and three CS—differential conditioning trials were then conductedin an irregular order (H 1 h ) , with an in-tertrial interval of 2 days. Each CS+ trial endedwith a .75 mEq/kg injection of .15 M lithiumchloride, and each CS— trial ended with a com-parable injection of physiological saline. For 29subjects a 2% vinegar solution served as the CSf,and a \% sodium chloride solution served as theCS—; for the remaining 29 subjects these flavorassignments were reversed.

Two to three days after the final conditioningtrial, each subject received a 120-min drinking testwith a 3% vanilla solution. For Group CS+ (n —15, eight with vinegar as CS+), the vanilla testoccurred IS min after the end of a S-min infusionexposure to the CS+ flavor, which was immediatelyfollowed by a 75 mEq/kg injection of .15 M lith-ium chloride. Group CS— (n = 15, seven withvinegar as CS+) was treated the same way asGroup CS+ except for being exposed to the CS—flavor before the vanilla test, and Group W (n =14, seven with vinegar as CS+) received a S-minoral infusion of tap water followed by .75 mEq/kglithium injection 15 min before the vanilla test. Incontrast to the above treatments, Group N (n =14, seven with vinegar as CS+) was placed in theinfusion chambers for 5 min but was not attached to

AFTEREFFECTS OF LITHIUM-CONDITIONED STIMULI 59

the infusion pump and did not receive any fluid in-fusions. However, Group N received a lithium in-jection IS tnin before the vanilla test, as the othergroups. One subject in Group CS+ developed asevere respiratory illness before the end of the ex-periment and had to be discarded.

Results

The cumulative amount each group drankduring successive 10-min periods of the va-nilla test is shown in Figure 4. Subjects ex-posed to the CS+ flavor before the vanillatest drank considerably more than any of theother groups. The intakes of Groups W andN were similar to one another, whereas GroupCS~ drank slightly less than these groups.

Evaluation of the total vanilla consumptionscores confirmed the existence of group dif-ferences, F(3, 49) =4.24, p < .01. Subse-quent comparisons with the Newman-Keulstest (p < .05, two-tailed) showed that GroupCS+ drank more than any of the othergroups, which did not differ from each other.

Discussion

The fact that lithium-injected subjects ex-posed to the CS+ drank more vanilladuring the test session than drug-treatedsubjects exposed to the CS— replicates asimilar difference between these conditionsobserved in Experiment 3. The present resultsalso help to identify the factors responsiblefor this difference. The vanilla consumptionof Groups W and N, which were exposed totap water or no fluids before the test session,was comparable with the intake of GroupCS —. This result indicates that exposure tothe CS— flavor did not result in less fluidintake than what would have occurred other-wise. Rather, the difference between GroupCS+ and Group CS— is attributable to in-creased drinking elicited by prior exposureto the drug-conditioned CS-K

The present observations of greater con-sumption after exposure to a lithium-con-ditioned CS+ than following exposure to theCS— flavor or tap water are strikingly simi-lar to comparable comparisons made in sub-jects tested without lithium treatment (Dom-jan & Gillan, 1977, Experiment 1). Itappears that whether or not subjects are in-

20

Q 15

10

5-

0J

;4-CS-

0 30 60 90 120MINUTES

Figure 4. Mean cumulative vanilla consumption inExperiment 4 during a test session started 15 minafter infusion exposure to the CS+ flavor (CS+),the CS- flavor (CS-), tap water (W), or nofluids (N). (All subjects were also injected with.75 mEq/kg lithium IS min before the vanilla test.)

jected with the drug, the CS+ stimulatesmore drinking than exposure to the CS— ortap water. This similarity is consistent withthe conclusion of Experiment 3 that lithiuminjection and lithium-conditioned stimulihave independent and opposite aftereffectson drinking.

Experiment 5

Experiments 3 and 4 demonstrated thatexposure to lithium-conditioned stimuli in-creases drinking even if subjects are injectedwith lithium before the test session and thatthis increased drinking effect subtracts fromthe suppression of drinking otherwise pro-duced by drug treatment. These results wereobtained after conditioning with a small doseof lithium (.75 mEq/kg). Furthermore, thetest drug doses used were also relativelysmall (.75-1.5 mEq/kg in Experiment 3 and.75 mEq/kg in Experiment 4). Althoughsuch low test doses produce significant dis-ruptions of drinking, the resultant intakesuppressions are not severe (Domjan, 1977).Thus, it remains to be seen whether the en-hanced consumption produced by exposureto lithium-conditioned stimuli is sufficientlyrobust to subtract from the disruptive effectson drinking of larger lithium doses. It is

60 M. DOMJAN, D. GILLAN, AND G. GEMBERLING

20n

1/1UJO

2o

•̂

**"/ x-*CS-Na

PCS+Li

.xCS-Li

0 30 60 90 120MINUTES

Figure 5. Mean cumulative vanilla consumption inExperiment 5 during a test session started 15 minafter infusion exposure to the CS+ or CS— flavor.(Groups CS+Na and CS—Na were injected withphysiological saline 15 min before the test, whereasGroups CS+Li and CS—Li were injected with2.25 mEq/kg lithium.)

also not yet known that larger lithium dosescan condition such drug-compensatory reac-tions. Some investigators (e.g., Woods &Shogren, 1972) have suggested that drug-compensatory responses to drug-paired stim-uli may occur only when conditioning isconducted with low doses of the drug. Ex-periment 5 was conducted to provide evi-dence relevant to these considerations. Ahigher dose of lithium (2.25 mEq/kg) wasused during the conditioning and test trialsthan what had been used in Experiments3 and 4.

Method

Twenty-three male and 19 female 50-60-day-oldSprague-Dawley rats were used in proceduresidentical to those of Experiment 2 in all unspecifiedrespects. After recovery from the cannula opera-tion and adjustment to a 23.5-hr daily water depri-vation schedule, subjects received four infusion-adaptation sessions conducted on successive days.Three CS+ and six CS— differential conditioningtrials were then conducted, with each CS+ trialfollowed by two CS— trials. The intertrial intervalwas 1 day. Each CS+ trial ended with a 2.25mEq/kg injection of .15 M lithium, and each CS—trial ended in a comparable injection of physiologi-cal saline. For 20 rats a 2% vinegar solutionserved as the CS+, and a \% sodium chloridesolution served as the CS—; for the remaining 22subjects these flavor assignments were reversed.

One to two days after the final conditioning trial,each subject received a 120-min drinking test witha 3% vanilla solution. Subjects were distributedamong four groups for this test session, the groupsbeing counterbalanced as closely as possible forsex and the assignment of the vinegar and sodiumsolutions as the CS+ and CS— stimuli. For GroupCS+Na (n — 10, 5 males and 5 with vinegar asCS+) the vanilla test occurred 15 min after theend of a 5-min infusion exposure to the CS+ flavor,which was immediately followed by a 2.25 mEq/kginjection of physiological saline. Group CS—Na(n~ 10, 5 males and 5 with vinegar as CS+) wastreated the same way as Group CS+Na except forbeing exposed to the CS— flavor before the va-nilla test. The remaining two groups were injectedwith 2.25 mEq/kg lithium 15 min before the va-nilla test. Group CS+Li (n = ll, 7 males and 5with vinegar as CS+) was exposed to the CS+solution just before being injected with lithium, andGroup CS—Li (n— 11, 6 males and 5 with vinegaras CS+) was exposed to the CS— before the druginjection.

Results

The cumulative amount of vanilla eachgroup drank during successive 10- min pe-riods of the 120-min vanilla test is presentedin Figure 5. Subjects that had not been in-jected with lithium prior to the test session(Groups CS+Na and CS~Na) drank con-siderably more than subjects that receivedthe pretest drug treatment (Groups CS+Liand CS~Li). However, whether or notlithium was administered, subjects drankmore after exposure to the CS+ flavor thanafter similar exposure to the CS- solution.

Analysis of the total vanilla consumptionof each group confirmed that subjects thathad been injected with lithium shortly be-fore the vanilla test drank significantly lessthan subjects that had received control in-jections, F(\, 38) =66.67, p < .01. Themain effect of which stimulus (CS+ orCS—) preceded the vanilla test was alsosignificant, F(\, 38) = 12.04, p < .01. How-ever, the interaction between these variableswas not significant, F(\, 38) = 2.22, p >.10.

Discussion

The lithium treatment administered shortlybefore the vanilla test in the present studyresulted in much less drinking than what had

AFTEREFFECTS OF LITHIUM-CONDITIONED STIMULI 61

been observed with lower drug doses in Ex-periments 3 and 4. However, even underthese circumstances, the increased consump-tion produced by prior exposure to the drug-conditioned CS + was not influenced bypresence or absence of drug treatment onthe test day. These results indicate that theindependence of the effects of drug treatmentand exposure to drug-conditioned stimuli ondrinking observed in Experiment 3 also oc-curs with high lithium doses which producemuch more severe disruptions of intake.

General Discussion

The present experiments have improvedour understanding of the increased drinkingthat occurs after exposure to lithium-condi-tioned stimuli in several important ways.Experiment 1 demonstrated that the in-creased drinking effect is not an artifact oftesting subjects with a novel, palatable drink-ing fluid and also showed that lithium-con-ditioned stimuli produce a biphasic change indrinking, with drinking suppressed at thestart of exposure to the conditioned stimulusand enhanced a long time after CS onset orexposure. Experiment 2 provided evidencethat the increased drinking aftereffect oflithium-conditioned stimuli is not a resultof instrumental reinforcement of the drinkingresponse produced by the scheduling of wateraccess after drug injections during condition-ing, and Experiments 3, 4, and 5 showedthat the increased drinking effect occurs evenif subjects are injected with lithium prior tothe test session. The results of Experiments3 and 5 also showed that lithium administra-tion and exposure to lithium-conditionedstimuli have independent and opposite after-effects: Lithium disrupts drinking, whereasprior exposure to lithium-conditioned stimuliincreases consumption.

The finding that some aspects of lithium-conditioned stimuli influence drinking in amanner opposite to the direct effects of lith-ium on ingestion is not surprising. Responsesconditioned by pharmacological uncondi-tioned stimuli are often opposite or compen-satory to the responses directly elicited bythese drugs (see Siegel, 1977a, for a re-

view). Siegel recently used this observationas the basis for a conditioning interpretationof the development of tolerance to morphine(Siegel, 1975, 1976, 1977b, 1978). Ac-cording to this view, drug tolerance developsbecause the stimuli that precede each drugadministration become conditioned to elicitdrug-compensatory reactions which subtractfrom the effects of the drug. Therefore, lessof a drug effect is predicted when the drug ispresented with stimuli that elicit the com-pensatory response, and such drug toleranceis not expected when the drug is presentedin the absence of the conditioned stimuli.Evidence in support of these and other pre-dictions of the conditioning model of mor-phine tolerance has been provided by Siegeland his associates and by Mitchell and hisco-workers (Adams, Yeh, Woods, & Mitch-ell, 1969; Ferguson & Mitchell, 1969; Kayan& Mitchell, 1969; Kayan, Woods, & Mitch-ell, 1969; Siegel, 1975, 1976, 1977b, 1978;Siegel, Hinson, & Krank, 1978).

The present findings that lithium-condi-tioned stimuli elicit changes in drinking thatare opposite to the direct effects of lithiumand that these drug-compensatory reactionscan subtract from the suppression of drinkingproduced by the drug are consistent with theconditioning model of drug tolerance pro-posed by Siegel. However, there is an im-portant respect in which the present resultsare not comparable with those of Siegel. Hisexperiments suggest that drug-conditionedstimuli produce unidirectional changes in be-havior and that the compensatory condi-tioned responses are elicited directly by theconditioned stimuli rather than occurringonly as aftereffects of these stimuli (e.g.,Siegel, 1972, 1978). Therefore, the biphasicchange in drinking that occurs with lithium-conditioned stimuli (Experiment 1) is notentirely in accord with the conditioned com-pensatory response model.

The biphasic nature of the conditioneddrinking response observed in the presentstudies is more consistent with the opponent-process theory of motivation (Solomon,1977; Solomon & Corbit, 1974). Accordingto this theory, stimuli such as drugs thatproduce strong affective changes have their

62 M. DOMJAN, D. GILLAN, AND G. GEMBERLING

effects by first activating a primary a pro-cess, which in turn elicits an opposing bprocess that has a longer latency, slower re-cruitment, and slower decay than the a pro-cess. Responses characteristic of the b pro-cess are assumed to predominate followingthe termination of the affect-arousing stimu-lus, whereas responses characteristic of thea process are assumed to predominate in thepresence of the stimulus, at least when thestimulus is novel.

It is assumed that both the primary a andthe opposing b process can be elicited byconditioned stimuli (Solomon, 1977). The aprocess can become conditioned only to stim-uli paired with the responses characteristicof the a state. In contrast, there are two waysin which the b state can occur with condi-tioned stimuli. It can be elicited directly byCSs that were previously paired with the bstate. Alternatively, opponent responses canbe mediated by conditioned stimuli as after-effects of conditioned a processes (Solomon,1977).

The present results may be interpreted interms of the mediated elicitation of the op-ponent process by conditioned stimuli notedabove. One has to assume that suppressionof drinking is characteristic of the a processassociated with lithium and that increaseddrinking is characteristic of the opponent bprocess. In our experiments, the CS+ wasconditioned by pairing it with the onset oflithium malaise. Thus, the primary processassociated with lithium should have becomeconditioned to the CS + . Consistent withthis assumption, drinking was suppressedin the presence of lithium-conditioned stim-uli. However, the opposite reaction, increaseddrinking, occurred when subjects were testedafter presentation of the CS + . This could beinterpreted as evidence for the mediated elici-tation of the opponent b process.

Although the effects of lithium-conditionedstimuli on drinking can be described in termsof conditioned opponent processes, it is notentirely clear that doses of lithium similarto those used in the present experiments re-sult in an unconditioned opponent processthat is reflected in increased drinking. Dom-jan (1977) failed to observe increased drink-

ing in rats tested starting as long as 120 minafter the injection of 1.8 mEq/kg lithium.However, increased drinking of water hasbeen observed in rats tested 8 hr after treat-ment with much larger lithium doses (Smithet al., 1970). It remains to be seen whethersuch delayed polydipsia also occurs withlithium doses that are more comparable withthose used in the present experiments.

The fact that lithium-conditioned stimulihave opposite effects on drinking during andafter their presentation is also relevant todiscussions concerning the nature of classi-cally conditioned responses. Pavlov's (1927)characterization of conditioned responses assimilar to responses elicited by the uncon-ditioned stimulus has been repeatedly re-futed and defended over the years (e.g., Hil-gard, 1936; Kimble, 1961; Mackintosh, 1974;Tolman, 1932). Experimental evidence hasnot helped to resolve this controversy be-cause in some situations the conditioned stim-ulus elicits responses opposite to thoseelicited by the US (e.g., Siegel, 1972). Inyet other experiments, the conditioned stim-ulus elicits some responses characteristic ofthe unconditioned response and other re-sponses that are compensatory to the uncon-ditioned response (e.g., Korol, Sletten, &Brown, 1966; Lang, Brown, Gershon, &Korol, 1966). It has been suggested thatwhether conditioned responses are similaror compensatory to the effects of the uncon-ditioned stimulus may depend on the involve-ment of instrumental contingencies in theconditioning procedure (Konorski, 1967) oron the intertrial interval used, the extent ofconditioning, and the specific neural effectsof the US (Wikler, 1973). The present ex-periments suggest that in addition to thesefactors, the response observed to a condi-tioned stimulus may also depend on whenthe observations are made. Responses simi-lar to the effects of the US may occur duringthe CS or as a short-latency response to theCS, whereas responses compensatory to theUS may be evident later.

Reference Note

1. Domjan, M., Gemberling, G. A., and Gillan,D. ]. Increased drinking following exposure to

AFTEREFFECTS OF LITHIUM-CONDITIONED STIMULI 63

lithium-conditioned taste cues: Effects of con-ditioning trials and drug dose. Unpublishedmanuscript, 1979.

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Received February 13, 1979 •