SYNAPSE 8:270-280 (1991)

Beta-Adrenergic Receptor Subtypes in the Basal Ganglia of Patients With Huntington’s

Chorea and Parkinson’s Disease CHRISTIAN WAEBER, MONIQUE RIGO, GIORGIA CHINAGLIA, ALPHONSE PROBST,

AND JOSE M. PALACIOS Preclinical Research, Saitdoz Pharma Ltd., CH-4002 Basel, Switzerland (C.W., M.R., J.M.P.), and

Department of Pathology, Division of Neuropathology, University of Basel, CH-4003 Basel, Switzerland (G.C., A.P.)

KEY WORDS Cellular localization, Autoradiography, Striatum, Glial cells, Neuro- degenerative disease

ABSTRACT The density of [12511iodo-cyanopindolol binding to beta-1 and beta-2 adrenergic receptors was studied in post mortem basal ganglia samples of Huntington’s chorea and Parkinson’s disease patients using autoradiography. Whereas no significant changes were observed in sections from Parkinson’s and Huntington’s chorea grade 2 patients, a nearly complete loss ofbeta-1 binding sites was observed in the basal ganglia of Huntington patients at later stages of the disease. The concentration of beta-2 receptors was increased by a factor 2 in the posterior putamen of all choreic cases. These results are consistent with the view that beta-1 receptors are predominantly located on a subpopula- tion of neurons which degenerate at late stages of Huntington’s chorea, while beta-2 receptors are present mainly on glial elements.

INTRODUCTION Ligand binding autoradiography has been used to

establish the regional distribution of the receptors for the known neurotransmitters in human brain post mor- tem samples (Palacios et al., 1986). Provided com- pounds with suitable selectivity exist, this technique has allowed the differential localization of subtypes of receptors to be determined. Adrenergic receptors have been initially subdivided in at least 4 classes (termed al , a2, p l , PZ), with different pharmacological profiles and signal transduction systems. (For reviews, see WiIIiams and Lefkowtiz, 1978). This classification is now widely established and has been further confirmed by the cloning and the sequencing of the genes coding for different adrenergic receptors. (For review, see ODowd et al., 1989).

Using several ligands both a- and p-adrenergic recep- tors have been characterized by binding assays in ho- mogenate preparations from human postmortem tissue (Cash et al., 1985; Sumners et al., 1983; Weinreich and Seeman, 1981; De Paermentier et al., 1989). Enna et al. (1977) have described the distribution of P-adrenergic receptors in homogenates of grossly dissected regions of the human brain and their alterations in neurological diseases (197613). A better anatomical resolution has been provided by the use of autoradiographic tech- niques using [12511iodopindolol (Reznikoff et al., 1986) and [12511iodocyanopindolol (Pazos et al., 1985). These 0 1991 WILEY-LISS, INC.

techniques have revealed the enrichment of p receptors in neostriatum, the neocortex and the hippocampal formation but do still not allow to establish the precise cellular localization of the labelled receptor. While in animals selective experimental lesions have been used in an attempt to circumvent this drawback (see Jonsson, 1981; Johnson et al., 19891, the investigation of human brain pathologies where selective cell populations are altered can provide useful information (see Palacios et al., 1989).

Huntington’s chorea and Parkinson’s disease are neu- rodegenerative disorders both characterized by losses of selective neuronal populations in the basal ganglia. Huntington’s chorea is a genetically determined disease with marked atrophy, neuronal loss and astrocytosis mainly affecting the striatum (Vonsattel, 1985; Bird, 1980). The main pathological features of Parkinson’s disease is the degeneration of the midbrain dopaminer- gic cells projecting to the striatum (Hornykiewicz, 1966). The locus coeruleus, origin of noradrenergic fi- bers innervating the forebrain (Moore and Bloom, 1979), has also been found to be neuropathologically affected in this disease (Bernheimer et al., 1973).

Received September 19,1990; accepted in revised form November 23,1990. Address reprint requests t o J.M. Palacios, Preclinical Research, Sandoz

Giorgia Chinaglia’s permanent address is Clinica delle Malattie Nervose e Pharma Ltd., CH-4002 Basel, Switzerland.

Mentali, University of Padua, Via Ginstiniani 5,35100 Padua, Italy.

B-ADRENERGIC RECEPTOR LOCALIZATION 271

The present study was therefore undertaken to inves- tigate the effects of these two disorders on the distribu- tion and density of P-adrenergic receptors in order to obtain some information about the cellular localization of these receptors in the human brain.

MATERIALS AND METHODS Brain tissue samples were obtained from 13 control

patients dying without reported neurological or psychi- atric disorders (6 males and 7 females, aged 66 ? 7; post-mortem delay: 12 t 3 h), from 8 subjects with Parkinson’s disease (5 males and 3 females, aged 81 ? 4; post-mortem delay: 21 _t 5 h) and from 10 sub- jects with Huntington’s chorea (4 males and 6 females, aged 59 k 6; post-mortem delay 20 * 4 h, five cases were classified as grade 2, 5 were classified as grade 3, according toVonsattel(1985)). The control cases and the specimen from patients with PD were provided by the Department of Pathology of the University of Basel. Specimens from some patients with Parkinson’s disease and from all patients with Huntington’s chorea were obtained from Prof. E. Bird at Harvard University.

Ten km thick sections were cut with a cryostat- microtome (Leitz 1720, Wetzlar, F.R.G.) and thaw- mounted onto gelatin-coated slides. The sections were kept at -25°C for several days or weeks before used. P-adrenergic receptors were labelled using [12511iodo- cyanopindolol (-2000 Ci/mmol; Amersham, UK). Sec- tions were brought to room temperature 30 min prior to a 10 min preincubation in 50 mM Tris- HCl buffer (pH 7.4) containing 150 mM NaC1. The sections were then incubated, still at room temperature, for 2 hours in the same buffer, supplemented with 110 pM [12511iodo-cyan- opindolol, 10 pM pargyline, 0.01% ascorbic acid, 0.3% bovine serum albumin. One hundred nM CGP 20712A and 70 nM ICI 118551 were used to block selectively [1251]i~do-cyan~pindolol binding to P l and 62 receptors, respectively. The concentration of these compounds were chosen to optimally discriminate between P l and p2 binding sites, taking into account their affinities for these sites in the human brain, as reported by De Paermentier et al. (1989). Nonspecific binding was esti- mated by adding 30 pM isoproterenol to the incubation medium. Furthermore, as [12511iodo-cyanopindolol is known to label some 5-HT1 receptor subtype (Hoyer et al., 1985), 10 FM 5-HT was used to assess the specificity of the P-adrenergic receptors labelling. After incuba- tion, sections were transferred to fresh buffer and washed twice for 10 min at room temperature. Finally, tissues were dipped in ice-cold distilled water to remove the salts and dried under a stream of cold air. Autora- diograms were generated by apposing the dry slides to 3H-Hyperfilms (Amersham, UK). Exposure time was 14 h at 4°C. After development, autoradiograms were analyzed and quantified with a computer-aided image analysis system (MCID Imaging Research Inc., St-Catharines, Ont., Canada), as previously described

(Waeber et al., 1989): images of brain regons to be analyzed were outlined. Their optical density was mea- sured and converted to fmol ligand/mg of tissue using 10 km thick polymer 1251-labelled microscales (Amersham, UK). One section was analysed per condition, brain region and individual. Sections consecutive to those incubated with [12511iodo-cyanopindolol were stained for acetylcholinesterase activity according to the method described by Geneser-Jensen and Blackstad (1971).

The effect of the different pathologies on the densities of P receptors were determined by oneway analysis of variance (ANOVA) followed by a Dunnett’s multiple comparison test. The null hypothesis (i.e. no difference between the mean value of control and pathology group) was rejected if the observed statistic was greater than the critical value for the q-statistic at an alpha error rate of 5%.

RESULTS In the control subjects, the highest density of total

[‘251]iodo-cyanopindolol binding was found in the cau- date nucleus, the nucleus accumbens and the putamen (Fig. 1; Table I). In these areas, the distribution of binding sites was heterogeneous.

Figure 2 shows that patches with higher densities of binding sites were mainly found in the putamen (Fig 2A), but their localization did not seem to coincide with that of high acetylcholinesterase activity (dark areas in Fig 2B). In the caudate and accumbens nuclei, some areas with lower densities of binding sites (Fig 2A, dark arrows) appeared to colocalize with putative ‘strio- somes’ (patches with low acetylcholinesterase activity (Graybiel, 1990), Fig 2B). The posterior part of the putamen appeared to contain less binding sites than its anterior and medial aspects. High densities of P-adren- ergic receptors were also observed in the insular cortex and the lateral segment of the globus pallidus (Table I). Areas presenting intermediate densities of sites were the medial segment of the globus pallidus and the substantia nigra pars reticulata. In the cerebellum, intermediate densities of binding sites were present both in the granule and molecular cell layers as well as in the dentate nucleus (Fig. 1).

In all these regions, 5-HT7 at a concentration of 10 kM, was not able to displace [1251]iodo-cyanopindolol binding, whereas the addition of 30 FM isoproterenol in

Abbreviations

Acc accumbens nucleus Cd caudate nucleus c1 claustrum c x cortex GP, globus pallidus pars lateralis

globus pallidus pars medialis % nucleus dentatus Put putamen

272 C . WAEBER ET AL.

Fig. 1. Autoradiograms obtained by apposing ['2511iodo-cyanopindoIol-labelled human tissue sections of the neostriatum (A-C) and cerebellum (D-F) to 3H-sensitive films. The addition of 10 FM 5-HT in the incubation medium has no effect on the intensity of labelling in these regions (B,E); whereas 30 pM isoproterenol displaces the radioligand from virtually a11 the binding sites in the neostriatum (C) with low non specific binding left in the cerebellum. Scale bar: 1 cm.

the incubation medium resulted in a level of labelling corresponding to that of background (Fig. 1). One hun- dred nM GCP 20712A (a p l selective drug) was a more potent displacer in the striatum (Fig. 3) than in the cerebellum (Fig. 41, whereas an inverse relation was observed using 70 nM ICI 118551 (g2 selective drug).

In control cases, no significant correlation was found between the intensity of p l and p2 labelling and param- eters such as gender, age and postmortem delay (data not shown). In subjects with Parkinson's disease, no significant alteration of total P-adrenergic sites was observed, akhough the density of pl-receptors was

slightly, but not significantly, decreased in the head of caudate nucleus (Figs. 5b and 6b; Table I). An increase of p2-receptors was apparent in the neostriatum, but with a low level of significance. An increase of the p2 receptors was also observed in the brain of Huntington patients of grade 2. Although this increase was more than twofold in the caudate body and middle third of the putamen, it was not significant in the Dunnett's test (Table I). A small reduction of p l binding sites was also measured in the anterior and middle thirds of the putamen and in the caudate body of Huntington grade 2 patients. This contrasted with the dramatic loss of p l

6-ADRENERGIC RECEPTOR LOCALIZATION

TABLE I. Densities of total p-adrenergic receptor binding, of binding remaining in the presence of 70 nM ICI 118551 and in the presence of 100 nM CGP 207124 in different areas of human brain*

Total binding Controls Parkinson Huntington I1 Huntington I1 Regions n mean ksem n mean f s e m n m e a n f s e m n m e a n i s e m

Dorsal caudate head 8 15.6 i 2.1 8 14.3 i 2.9 2 28.9 f 5.3 3 10.5 i 2.2 Ventral caudate head 8 24.7 3.6 8 22.0 f 3.7 3 28.6 f 10.6 3 12.3 i 2.8 Putamen ant. third 11 26.6 +3.2 8 25.6 f 3 . 4 4 25.3 F 2.2 3 13.7 i 1.4 Accumbens 7 34.0 f 5.8 8 33.8 f 5.1 2 49.9 f 10.5 Caudate body 8 21.0 k 3.4 6 14.1 f 4.3 3 11.2 i 3.8 Putamen middle third 8 29.2 f 2.7 8 26.1 i 3.9 3 30.4 i 6.5 3 16.9 f 4.8 Putamen post. third 7 19.1 i 1.8 8 2 3 . 5 i 3.0 4 1 5 . 6 i 2.8 5 8.5 * 1.0 Globus pallidus lat. 7 13.8 k 1.6 8 11.8 * 3.1 2 9.5 zk 2.1 3 10.2 * 2.5 Globus pallidus med. 7 18.7 i 2.5 8 16.8 f 3.0 2 1 1 . 8 i 1.0 3 9.8 f 1.7 Insular cortex 9 13.3 2.1 8 14.5 f 2.1 3 21.8 F 1.9 3 12.2 k 0.4 S. nigra reticulata 7 11 .0f2 .7 5 7 .9k1 .1 2 1 1 . 9 i 0 . 5 3 22 .6 i9 .7 S. nigra compacta 7 9.1 f 1.9 4 7.2 i 1.1 2 18.8 f 6.1

273

+ ICI 118551

Dorsal caudate head Ventral caudate head Putamen ant. third Accumbens Caudate body Putamen middle third Putamen post. third Globus pallidus lat. Globus pallidus med. Insular cortex S. nigra reticulata S. nigra compacta

n m e a n i s e m n m e a n I s e m n

8 14.8 * 2.6 8 8.2 I 1.6 2 8 23.3 i 3 . 5 8 14.0 f 2.3 3

11 22.3 f 3.2 8 18.6 f 2.4 4 7 31.3 * 4.7 8 26.1 f 3.8 2 8 14.6 f 2.6 6 10.8 i 2.2 3 8 26.2 1 4 . 0 8 20.1 f 3.1 3 7 13.4 i 1.8 8 15.3 f 1.5 3 7 7.3 i 1.4 8 5.6 f 2.3 2 7 11.1 i 2.0 8 9.2 i 2.2 2 9 8.7 f 1.8 8 8.6 f 1.5 4 6 8.1 i 3.5 5 2.4 i 0.3 2 6 4.7 i 1.9 4 1.9 f 0.6

+ CGP 207121 n m e a n i s e m n mean *sem n

m e a n f s e m n

13.3 F 2.0 3 14.1 f 5.8 3 15.6 f 1.4 3 25.7 f 3.3 7.4 k 0.2

15.9 1 5 . 7 3 14.5 f 5.7 4 5.0 f 1.1 3 7.6 i 0.6 3 9.3 f 1.4 3 5.9 i 1.5 2

mean + sem

Dorsal caudate head Ventral caudate head Putamen ant. third Accumbens Caudate body Putamen middle third Putamen post. third Globus pallidus lat. Globus pallidus med. Insular cortex S. nigra reticulata S. n i a a comuacta

8 8

11 7

2.8 f 0.4 3.6 10 .7 4.1 f 0.5 4.1 f 0.8 3.7 rt 0.3 3.2 * 0.3 3.8 + 0.6 4.9 f 0.8 5.3 f 0.7 5.0 f 0.9

10.9 f 3.1 8.4 k 2.0

8 8 8 8 6 7 8 8 8 7 5 4

'Values are given in fmol/mg protein i SEM. thdicates P < = 0.05 in Dunnett's multiple comparison test.

binding sites observed in all areas of the striatum of patients with Huntington's chorea, grade 3 (Figs. 5c and 6d; Table I). This reduction was accompanied by an increase in the number of 62 binding sites in the ante- rior and posterior thirds of the putamen, statistical significance was only reached for the latter region. The oneway analysis of variance performed on the density of p receptors in the nucleus accumbens, the insular cortex and the substantia nigra (both pars reticulata and pars compacta) did not reveal any significant differences between the control and the pathology groups.

DISCUSSION These results validate the use of ['2511iodo-cyanopin-

dolol to label p-adrenergic receptors in the human brain. This ligand has also been used to study serotonin 5- HTIB receptors in the rat brain (Hoyer et al., 1985), but

3.5 i 0.8 2 3.6 f 0.9 3 5.8 i 1.1 3 6.7 f 1.0 6.4 i 1.9 2 5.6 f 0.8 5.1 f 0.5 3 4.5 f 1.2 5.1 f 1.3 6.0 f 1.3 2 4.4 * 1.0 2 4.1 i 0.4

4.2 i 0.2 3.7 * 1.8 5.9 * 1.0

7.5 i 0.8

7.7 f 0.7

7.0 f 2.0 8.7 F 5.5

n

3 3 3

-

mean f sem

0.6 i 0.4t 2.9 f 0.8t 4.5 f 1.8t

6.2 F 2.3t 2.5 f 0.7t 1.9 * 0.9 2.1 i 1.0 2.9 i 0.6 4.5 f 4.5

mean f sem

4.6 f 2.4 5.7 i 1.9 7.2 f 0.5

3.5 f 1.8 8.9 f 2.5t 5.1 f 1.8 6.4 f 1.1 7.5 i 2.8 5.2 f 2.5

the presence of these sites has never been convincingly demonstrated in the brain of other species (Hoyer et al., 1986; Martial et al., 1989; Waeber et al., 1989; but also Biegon and Whitaker-Azmitia, 1987). This is further confirmed by the lack of effect of 10 pM 5-HT on [12511iodo-cyanopindolol binding in the present study. The distribution ofthe p adrenergic sites labelled by this ligand in the human brain is fully consistent with the one described in previous studies, p l receptors being most enriched in the neostriatum and the globus palli- dus and p2 sites predominating in the cerebellum (Pazos et al., 1985). This regional distribution is similar to that seen in rat (Palacios and Kuhar, 1982; Rainbow et al., 1984) and baboon brain (Slesinger et al., 1988).

The most striking finding of the present study is the nearly complete loss of pl receptors in the striatum of patients with late stage Huntington's chorea (grade 3).

274 C . WAEBER ET AL.

Fig. 2. Distribution of p adrenergic receptors compared to that of acetylcholinesterase activity in the human neostriatum. A is a nega- tive picture of an autoradiogram generated as described in material and methods, white areas are regions enriched in binding sites. B is a consecutive section stained for acetylcholinesterase activity according to the method described by Geneser-Jensen and Blackstad (1971) and

used as a negative to obtain this picture. ‘Striosomes’ are areas with low enzymatic activity (Graybiel, 1990) and appear darker. Black arrows point to ‘striosomes’ where the density of p receptors is low; they predominate in the caudate and accumbens nuclei. White arrows indicate ‘striosomes’ which do not coincide with reBons containing lower densities of binding sites. Scale bar: 5 mm.

Interestingly, p l binding sites were well preserved in the striatum of patients with Huntington’s disease grade 2. This could indicate that the major part of neostriatal p l receptors is located somato-dendritically on neurons which degenerate at late stages of the disease. A correlation between neuronal loss (patholog- ical grade according to Vonsattel et al., 1985) and biochemical parameters such as decreased concentra- tions of substance P (Beal et al., 1988) or choline acetyl- transferase (ChAT) (Ferrante et al., 1987) has already been reported; in the latter study, there was no alter- ation of ChAT activity in the putamen of moderate (grade 2 and 3) cases of Huntington’s disease, in con- trast to the loss observed in the putamen of severe (grade 3 and 4) cases. Such a pattern is similar to that observed in the present study, and has also been re- ported for benzodiazepine and GABA binding sites in the putamen (Walker et al., 1984) and for muscarinic

binding sites in the globus pallidus (Palacios et al., 1990) of pathologically graded cases of Huntington’s disease. Reiner et al. (1988) have shown that striatal substance P-containing neurons are less affected than enkephalin-containing cells at early and middle stages of the disease. This could indicate that striatal p l receptors are preferentially located on the former class of neurons. As neurons whose cell bodies are located in the globus pallidus and substantia nigra are not af- fected by the disease process ofHuntington’s chorea, the decrease of p l binding sites in these nuclei could be explained by a localization of these receptors on the neostriatal terminals in these areas. In a previous study the concentration of p receptors was shown to be normal in the caudate and putamen of subjects with Hunting- ton’s chorea (Enna et al., 1976a, 1976b), but signifi- cantly decreased in the globus pallidus. Several expla- nation can be proposed to explain the discrepancy

p-ADRENERGIC RECEPTOR LOCALIZATION 275

Fig. 3. Characteristics of [1251]iodo-cyanopindolol binding in the human striatum and globus pallidus. A shows labelling obtained with this compound in the absence of blocking drug. Very low and homoge- neous non specific binding was obtained by incubating consecutive sections in the presence of 30 FM isoproterenol (B). The addition of the

p2 selective drug ICI 118551 (70 nM) did not affect [1”511iodo-cyanopin- dolol binding, indicating that the majority of P-adrenergic receptors are of the pl subtype in these nuclei (C). This is confirmed by the fact that 100 nM CGP 20712A (a p l selective drug) leaves only a low level of p2 labelling in the human basal ganglia (D). Scale bar: 1 cm.

276 C. WAEBER ET AL.

Fig. 4. Characteristics of t12511iodo-cyanopindolol binding in the human cerebellum. Total binding is displayed in A, nonspecific binding is shown in B; the level of the latter is higher in the dentate nucleus than in the surroundingwhite matter. The p2 selective compound ICI 118551 (C) is more effective than the p l agent CGP 20712A(D) at displacing [1251]iodo-cyanopindolol binding in the cerebellum. Scale bar: 1 cm.

between these and our study. First, Enna et al. did not attempt to classify their Huntington's cases according to neuropathological severity; thus a decrease of P-recep- tors in advanced stages could have been masked by including patients of grade 1 or 2 in the study. Second,

there was no attempt to differentiate between subtypes of P-adrenergic receptors. As shown by our own data, receptor losses are much less impressive when p l and p2 receptor subtypes are considered together, owing to the differential changes affecting both receptor popula-

P-ADRENERGIC RECEPTOR LOCALIZATION 277

Fig. 5. Total [‘251]iodo-cyanopindolol binding in the neostriatum of a control case (A), in a Parkinson’s patient (B) and a Huntington grade 3 subject (C). A slight decrease of labelling density can be observed in the Parkinson patient, while a more pronounced decrease was found in the patient with Huntington chorea. Scale bar: 1 cm.

tions. These considerations could also explain why Zah- niser et al. (1979) did not observe any change in (3 receptor densities after kainic acid application to the rat striatum. This neurotoxin provokes comparable, though less selective (Beal et al., 1986), cell losses than those occurring in Huntington’s chorea and has been proposed as a model for this pathology (Coyle and Schwarcz, 1976). Confirmingour finding, Nahorski eta]. (19791, as well as Chang et al. (1980), found a significant 20-30% decrease in binding of the pl subtype in this area using a similar experimental approach.

Slightly increased densities of p2 receptors in grade 2 and 3 could result from binding sites being expressed by cells remaining intact in Huntington’s chorea and from increased package density of cells due to tissue shrink- age. Such an explanation has already been proposed for the increased densities of NADPH-diaphorase positive striatal neurons, for instance (Ferrante et al., 19871.82 receptors could be localized on astrocytic cells, whose number has been reported to be increased in the neostri- atum of Huntington’s chorea patients (Vonsattel et al., 1985).

The density of pl receptors was not significantly a1 tered in Parkinson’s disease patients, although a trend to a decrease was observed in the neostriatum. This result indicates that the majority of p l receptors is unlikely to be located on, or to be modulated by, nigrai dopaminergic neurons projecting to the striaturn. A 30% decrease of rat striatal j3-receptors has also been re- ported after a 6-hydroxydopamine lesion of the nigro-

striatal pathway (Reisine et al., 1979), a finding sug- gesting that at least some (3-receptors in the striatum of this animal are located on dopaminergic projections to this nucleus. Such a hypothesis could also explain the slight decrease of p l receptors we observe in the neostri- atum.

8-adrenergic receptors have been previously studied in the prefrontal cortex of Parkinson’s disease subjects (Cash et al., 1984, 1986; D’Amato et al., 1987) and in several areas of the rat brain after 6-hydroxydopamine lesions of the locus coeruleus (Cash et al., 1986). The density of p-adrenergic receptors was found to be in- creased in the rat cortex, but was unaltered in the striaturn. Consistent with the finding in the rat cortex, an increase of (31-receptors was found in the cortex of patients with Parkinson’s disease in the studies of Cash and colleagues while no alteration was observed by D’Amato and colleagues. Subcellular fractionation per- formed by Cash et al., (1986) suggested that 8 receptors are Iocated on non adrenergic nerve terminals, while PZ receptors might be situated on glial cells.

The fact that the density of p l receptors increases in the prefrontal cortex but not in the basal ganglia of Parkinson’s disease patients supports the assumption that alterations in the noradrenergic system may be involved in cognitive impairment rather than in motor disorders (Pillon et al., 1989). In fact, increased p l binding tended to be more pronounced in patients with Parkinson’s disease and dementia (Cash, 1984). Corti- cal and striatal p receptors might be controlled by

278 C. WAEBER ET AL.

Fig. 6. Total ['251]iodo-cyanopindolol binding in the neostriatum and globus pallidus in a control case (A), a Parkinson patient (B), a case with Huntington's chorea grade 2 (C) and grade 3 (D). The slight decreases observed in Parkinson patient and in Huntington patient grade 2 are not significant, whereas in the Huntington patient grade 3, the concentration of p receptor binding sites is dramatically altered. Scale bar: 1 cm.

6-ADRENERGIC RECEPTOR LOCALIZATION 279

different mechanisms and could therefore react differ- ently to decreased noradrenergic innervation (Scatton et al., 1983), as observed in Parkinson’s disease.

CONCLUSIONS Our results in Huntington’s chorea indicate a local-

ization of p l receptors on a subpopulation of striatal neurons, as well as on their projections to the globus pallidus and the substantia nigra. Increased concentra- tions of p2 binding sites observed in Huntington’s cho- rea corroborate the assumption that glial elements could bear these receptors. The fate of striatal p recep- tors in Parkinson’s disease indicate that the majority of these sites are not located on nigral dopaminergic neu- rons. Finally, striatal and cortical p adrenergic recep- tors seem to be differently affected in Parkinson’s dis- ease.

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