PSYCHIATRY AND PRECLINICAL PSYCHIATRIC STUDIES - ORIGINAL ARTICLE

Diurnal rodents as an advantageous model for affective disorders:novel data from diurnal degu (Octodon degus)

Tal Ashkenazy-Frolinger • Haim Einat •

Noga Kronfeld-Schor

Received: 21 October 2013 / Accepted: 6 December 2013

� Springer-Verlag Wien 2013

Abstract Circadian rhythms are strongly associated with

affective disorders and recent studies have suggested uti-

lization of diurnal rodents as model animal for circadian

rhythms-related domains of these disorders. Previous work

with the diurnal fat sand rat and Nile grass rat demonstrated

that short photoperiod conditions result in behavioral

changes including anxiety- and depression-like behavior.

The present study examined the effect of manipulating day

length on activity rhythms and behavior of the diurnal

degu. Animals were housed for 3 weeks under either a

short photoperiod (5-h:19-h LD) or a neutral photoperiod

(12-h:12-h LD) and then evaluated by sweet solution test

and the forced swim test for depression-like behavior, and

in the light/dark box and open field for anxiety-like

behavior. Results indicate that short photoperiod induced

depression-like behavior in the forced swim test and the

sweet solution preference test and anxiety-like behavior in

the open field compared with animals maintained in a

neutral photoperiod. No effects were shown in the light/

dark box. Short photoperiod-acclimated degu showed

reduced total activity duration and activity was not

restricted to the light phase. The present study further

supports the utilization of diurnal rodents to model

circadian rhythms-related affective change. Beyond the

possible diversity in the mechanisms underlying diurnality

in different animals, there are now evidences that in three

different diurnal species, the fat sand rat, the grass Nile rat

and the degu, shortening of photoperiod results in the

appearance of anxiety- and depression-like behaviors.

Keywords Animal model � Circadian rhythm �Anxiety � Depression � Diurnal � Nocturnal

Introduction

Circadian rhythms abnormalities are clearly involved in the

pathology of mood disorders such as major depressive

disorder (MDD), bipolar disorder (BPD) and seasonal

affective disorder (SAD) (Kronfeld-Schor and Einat 2012;

McClung 2007; Nestler et al. 2002; Lenox et al. 2002; Lam

and Levitan 2000). Affective disorder symptoms show

diurnal variations (Gordijn et al. 1994), and treatments

directed to affect the circadian system, such as bright light

therapy, phase-advance therapy and sleep deprivation,

contribute to the remission on these illnesses, sometimes

even in drug-resistant patients (Dietzel et al. 1986; Kripke

1998; Yamada et al. 1995; Wirz-Justice and Van den

Hoofdakker 1999; Giedke and Schwarzler 2002; Wehr

et al. 1979; Wu et al. 2009; Moscovici and Kotler 2009;

Benedetti et al. 2001). Manipulating light exposure affects

several neurotransmitter systems related to mood including

dopamine (Abılio et al. 1999; Abılio et al. 2003), serotonin

(Zawilska et al. 1997) and noradrenaline (Zubidat et al.

2007). Antidepressants and mood stabilizers are known to

affect pathways related to the circadian system including

melatonin receptors, serotonin levels, sleep architecture

and hormone secretion (Jawed et al. 2007; Sonntag et al.

T. Ashkenazy-Frolinger � N. Kronfeld-Schor (&)

Department of Zoology, Tel-Aviv University, Ramat-Aviv,

69978 Tel Aviv, Israel

e-mail: nogaks@tauex.tau.ac.il

H. Einat

School of Behavioral Sciences, Tel Aviv-Yaffo Academic

College, Tel Aviv, Israel

H. Einat

Department of Clinical Biochemistry and Pharmacology,

Ben-Gurion University of the Negev, Beersheba, Israel

123

J Neural Transm

DOI 10.1007/s00702-013-1137-3

1996; Wirz-Justice et al. 1980; Tan et al. 2007). Addi-

tionally, human genetic association studies implicate clock

genes in mood disorders (Benedetti et al. 2003; Johansson

et al. 2003; Partonen et al. 2007) and animal studies

demonstrate affective-like behavioral changes related to

targeted mutations in clock genes (Bunney and Bunney

2000; Roybal et al. 2007; Le-Niculescu et al. 2008).

Recently, a disruption of the circadian pattern of gene

expression in several brain areas was described in major

depressive disorder (Li et al. 2013).

Circadian rhythms are driven by an internal master

circadian clock, which in mammals is located in the sup-

rachiasmatic nucleus (SCN) in the hypothalamus, and

subsidiary clocks in nearly every body cell (Dibner et al.

2010). The SCN is entrained to the environment, with light

acting as the strongest synchronizer. A disruption of the

circadian clock results in misalignment between the inter-

nal circadian clock and the activity pattern, which may

have adverse consequences such as metabolic syndrome,

obesity, insomnia, increased risk of cancer, as well as other

physiological and mental disorders (Albrecht 2010; Arble

et al. 2009; Karatsoreos et al. 2011; Scheer et al. 2009).

Animal models are critical in our attempts to understand

the pathophysiology of affective disorders and develop

better medications (Einat 2010; Tallman 1999; Tecott and

Nestler 2004). Significant advances in research were made

by selecting homologous model animal, including the use

of non-traditional model animals, to explore a variety of

biological systems in the context of health and disease

(Kara and Einat 2013; Smale et al. 2005; Bolker 2012).

Previous studies from our laboratories suggest that it is

possible that some of the difficulty in the identification and

development of good animal models for circadian rhythm

disturbances-related psychiatric diseases in humans is that

the standard animals used for modeling neuropsychiatric

research are nocturnal rodents and that there might be an

advantage in developing models utilizing diurnal animals

(Einat and Kronfeld-Schor 2009; Kronfeld-Schor and Einat

2012).

Despite the extraordinary advancement in our under-

standing of the circadian clock mechanism, it is still unclear

how the temporal signals from the clock are translated into

activity patterns, and how they differ in diurnal and nocturnal

mammals (Cohen et al. 2009; 2010a; Hagenauer and Lee

2008; Smale et al. 2008). Nevertheless, it is clear that some

fundamental differences exist between nocturnal and diurnal

mammals (Challet 2007; Cuesta et al. 2008; Smale et al. 2008),

which may be crucial for the study of circadian rhythms-

related diseases. For example, like humans, diurnal species are

active when melatonin levels are low, while nocturnal mam-

mals are active when melatonin levels are high (Nowak and

Zawilska 1998). Melatonin decreases anxiety-like behavior in

nocturnal species, while in diurnal species it decreases it, or

has no effect on anxiety (Bilu and Kronfeld-Schor 2013).

Another important component of the circadian system is the

masking effect of light. Specifically, light increases activity in

diurnal mammals (positive masking) and suppresses it in

nocturnal ones (negative masking), while darkness acts in

opposite ways (Cohen et al. 2010b; Hagenauer and Lee 2008;

Rotics et al. 2011; Barak and Kronfeld-Schor 2013; Shuboni

et al. 2012). Because of these significant differences, we pre-

viously suggested the utilization of diurnal rodents as model

animals to decipher the mechanisms underlying the relation-

ship between circadian rhythms and affective behavior

(Kronfeld-Schor and Einat 2012). In accordance with this

suggestion, several studies found that, indeed, a model based

on diurnal rodents demonstrates relatively strong validity for

the exploration of photoperiod-related affective changes.

Specifically, sand rats (Psammommys obesus) and Nile grass

rats (Arvicanthis Niloticus) exposed to 3 weeks or more of

short photoperiod (5-h:19-h LD) show anxiety- and depres-

sion-like behaviors (Einat et al. 2006; Ashkenazy et al. 2009b;

Ashkenazy-Frolinger et al. 2009; Leach et al. 2013a). More-

over, similar anxiety- and depression-like symptoms were

induced by administration of melatonin in a regimen that

mimics short photoperiod (Ashkenazy et al. 2009b), and

ameliorated after clinically relevant treatment with bright light

or antidepressants (Ashkenazy et al. 2009a; Krivisky et al.

2011, 2012). These results strongly support the possible use of

diurnal animals to model circadian rhythms-related affective

disorders in humans.

Because the ancestral state of mammals is nocturnality and

diurnality has evolved in several independent events (Roll

et al. 2006), it is possible that diurnality, and the mechanisms

underlying it, are diverse. Therefore, to fully understand di-

urnality and its relation to affective disorders, it is important to

study several unrelated species of diurnal rodents. To date, the

fat sand rat and the Nile grass rat were studied in this context

and the present study was designed to examine a third diurnal

rodent, the degu (Octodon degus), a highly social, diurnal, rat-

sized rodent from central Chile. Degus have been used in a

number of study areas including circadian rhythms research

(Lee 2004), separation distress, social attachment and play

(Colonnello et al. 2011a), but not in the context of depression.

The present study therefore evaluated the effects of short

photoperiod conditions on activity rhythms and affective-like

behavioral tests in the degu.

Materials and methods

Animals

Adult male degu (*4–6 mo old), weighing approximately

200 ± 20 g at the start of the experiment from our

breeding colony at the I. Meier Segals Garden for

T. Ashkenazy-Frolinger et al.

123

Zoological Research at Tel Aviv University were used for

the experiments. Degus were divided into two groups

(n = 8 per group) and individually housed in standard

plastic cages (21 9 31 9 13 cm) in two different temper-

ature-controlled rooms under 12-h:12-h LD (lights on at

08:00 h, neutral photoperiod, NP, 800 Lux,). Under labo-

ratory conditions degus are diurnal when maintained at

17–22 �C. When housed at higher temperatures, many

animals are crepuscular and some are even nocturnal

(Kenagy et al. 2002b; Lee 2004). Therefore, we kept them

at 20 �C. Degus were provided with ad libitum rodent

chow (product 19560 by Harlen, Jerusalem, Israel) and

water, and were weighed 1 week after arrival (week 1) and

once a week thereafter for a period of 6 weeks. All pro-

cedures were conducted in accordance with and approved

by the Institutional Animal Ethics Committee (13-004-L).

All efforts were made to minimize the number of animals

used and their discomfort.

Experimental procedure

Photoperiod manipulation

After a week of acclimatization to the housing conditions,

the photoperiod of the test group was changed to 5-h:19-h

LD (lights on at 08:00 h, short photoperiod, SP, 800 Lux).

This lighting regime was set based on previous results with

fat sand rats (Einat et al. 2006; Ashkenazy et al. 2009b, b)

and Nile grass rats (Ashkenazy-Frolinger et al. 2009; Leach

et al. 2013b). Degus remained under these conditions for

3 week prior to onset of experiments, a time that is suffi-

cient for physiological acclimation (Kronfeld-Schor et al.

2000) and synchronization of circadian rhythms (Cohen

and Kronfeld-Schor 2006; Kronfeld-Schor et al. 2001) and

was previously shown to be adequate for the induction of

anxiety- and depression-like behaviors in the fat sand rat

(Einat et al. 2006; Ashkenazy et al. 2009b) and in the

Nilegrass rat (Ashkenazy-Frolinger et al. 2009). The initial

number of animals per group was eight, but two degus from

the SP group were not tested because they lost over 20 %

of body weight during acclimation time.

Behavioral testing

Behavioral experiments: general Animals were tested in

a battery of behavioral tests as detailed below. To minimize

the effects of behavioral experience on results, experiments

were conducted from the less to the more intrusive. The

order of experiments was: (1) home cage continuous

activity monitoring; (2) sweet solution preference; (3)

light/dark box; (4) large open field exploration; (5) forced

swim test. With small variations, this battery was previ-

ously used with the fat sand rats and the grass Nile rats

(Ashkenazy-Frolinger et al. 2009). Animals were tested

one test per day (except the sweet solution preference test

which is longer) as detailed below. All behavioral tests

were performed during the light hours of both groups and

in a group balanced manner. Experiments started at least

30 min after ‘‘lights on’’ and were terminated no later than

30 min before ‘‘lights off’’. For the SP group, experiments

were performed between 08:30 and 12:30 h, well within

the light/activity phase of the two groups and were there-

fore preformed in the light (800 lx).

Activity monitoring Activity of the two groups was con-

tinuously recorded using an infrared detector (Intrusion

detector model MH10, Crow group, Kiriat Reufa, Israel)

placed above their cages and connected to a PC. Data were

collected at 6-min intervals using software designed for

this purpose (ICPC, Ntanya, Israel) from the beginning of

the acclimation period until the end of all experiments.

Sweet solution preference Anhedonia is a core symptom

of depression (Sadock and Kaplan 2007) and can be

evaluated in animals using the sweet solution preference

test (Papp et al. 1991). Animals were supplied with a bottle

of 2 % sucrose solution (SIGMA, Rehovot, Israel) dis-

solved in tap water, on top of the regular supply of water

and food. The sucrose concentration was selected based on

previous experiments with degus (Colonnello et al. 2011b).

The weights of sucrose solution and water bottles were

taken at the beginning of the experiment and every 24 h

thereafter, approximately 4 h after ‘‘lights on’’. Sweet

solution preference was calculated daily as a ratio of

sucrose solution consumption out of total liquid (sucrose

solution ? water) consumption. This computation is nec-

essary to overcome weight variability between individual

animals or possible generalized effects on liquid con-

sumption (Flaisher-Grinberg et al. 2009). The schedule

included 5 days of continuous exposure to sucrose (‘‘day

1’’ representing preference for hours 0–24, ‘‘day 2’’ rep-

resenting preference for hours 24–48, ‘‘day 3’’ representing

preference for hours 48–72, ‘‘day 4’’ representing prefer-

ence for hours 72–96, ‘‘day 5’’ representing preference for

hours 96–118).

Light/dark box The light/dark box test is a frequently

used test for anxiety-like behavior (Crawley 2007). For the

current experiment, the light/dark box was constructed

from Plexiglas box (60 cm 9 25 cm with 30 cm walls)

and divided into two compartments: black, covered com-

partment (dark, one-third of the box) and white, uncovered

compartment (light, two thirds of the box) with a separat-

ing wall that is slightly ajar to allow free transitions

between the compartments. Each degu was placed in the

light part of the box and allowed to freely move for a 5-min

Short photoperiod in diurnal degu

123

session. Behavior was digitally recorded from an overhead

camera interfaced with a computer for later analysis and

manually scored from recordings for measures of time and

frequency of visits to the white part of the box. An animal

was considered to be in one of the compartments when its

head and the two front paws were in that area of the box. At

the end of the session, animals were returned to their home

cages and the box was wiped clean with a 10 % alcohol

solution.

Open field The open field is a widely used test in animal

psychobiology research (Walsh and Cummins 1976). In this

test, an animal (usually a rodent) is introduced into a plain

and illuminated arena (Genaro and Schmidek 2000) and its

behavior in the arena is regarded as a fundamental index of

general activity (Walsh and Cummins 1976) and anxiety

(Prut and Belzung 2003). Each degu underwent a 20-min

open field test in a 1 m 9 1 m arena with 40-cm high walls.

A video camera was mounted above the arena and inter-

faced with a video tracking computer program (Ethovision,

Noldus, The Netherlands). This program provides a number

of behavioral measures including measures of the amount

and the distribution of activity. At the end of each session,

animals were returned to their home cages and the area was

wiped clean with a 10 % alcohol solution.

Forced swim test The forced swim test is possibly the

most frequently used test for antidepressant effects of

manipulations and treatments (Martijena et al. 1996; Cryan

and Holmes 2005) and is a commonly used test for

depression-like behavior in both rats and mice, and was

also utilized in other rodents with some methodological

difference in application across species (Porsolt et al. 1978;

Wallace-Boone et al. 2008; Ashkenazy et al. 2009a, b;

Ashkenazy-Frolinger et al. 2009). For the current study, the

test was performed in a white, opaque plastic cylinder,

30 cm in diameter and 45 cm in height. The cylinder was

filled with water (21–23 �C) to a depth of 25 cm, pre-

venting the degus from touching the floor or escaping. A

digital video camera was mounted above the cylinder and

recorded files were later used to score behaviors. Animals

were tested in alternating order of the two groups, with

each animal individually placed in the water by the

experimenter and left there to swim. Similarly to what we

previously observed in the sand rats (Einat et al. 2006;

Ashkenazy et al. 2009a, b; Ashkenazy-Frolinger et al.

2009), degus are not as good swimmers as rats and mice

and they cannot float well. Therefore, when they reach the

state when they do not swim or struggle, they sink into the

water. Because this behavior is similar to what we previ-

ously reported in the sand rats, we followed the previously

established sand rat protocol (Einat et al. 2006; Ashkenazy

et al. 2009a, b; Ashkenazy-Frolinger et al. 2009). In this

protocol, the main measure is the first and second events of

‘time to sink’ where sinking is defined as a time when the

entire body of the animal (including snout) is immersed in

water. After two sinking events animals were taken out of

water, dried with a paper towel and replaced in their cages.

According to this protocol, in the rare event that an animal

sinks and stays under water for 5 s, it is immediately

removed from the water by the experimenter; however, no

such events happened in the present experiment.

Statistical analysis Continuous activity data were col-

lected at 6-min intervals and analyzed for phase preference,

activity profile (averages of activity levels in 6-min inter-

vals over a 24-h periods), activity onset and offset (esti-

mated using a template matching algorithm, searching for

6-h period of inactivity followed by a 6-h period of high

activity for activity onset, and 6-h period of high activity

followed by a 6-h period of inactivity for activity offset)

using the Clocklab program (Actimetrics Wilmette, IL)

that was also used to generate all actograms. Activity onset

and offset values were compared between the groups using

an unpaired t test, and within the same group at different

time points using a paired t test, using Statistica 7.0 soft-

ware (Statsoft, Tulsa, OK, USA). Duration of activity was

defined as the time between activity onset and offset.

Data from all other experiments were analyzed using an

analysis of variance (ANOVA) with Statistica 7.0 software

(Statsoft, Tulsa, OK, USA). Data for the weights, sweet

solution preference test and FST were analyzed with

repeated-measures ANOVA with photoperiod length as the

main factor and week (weight), day (sweet solution pref-

erence) or ‘‘sink’’ (FST) as a repeated-measure factor.

When the ANOVA resulted in a significant effect, it was

followed by a separate t test analysis for each repetition.

Specifically, for weight the data were analyzed separately

for each weighing, for the sweet solution preference test

the data were analyzed separately for each day and for the

FST the data were analyzed separately for each ‘‘Sink’’

event (Sink 1 and Sink 2).

The light/dark box and open field experiments were ana-

lyzed using t test analysis with photoperiod as the main

factor. For all experiments, the level of statistical significance

was set at p \ 0.05. Data are presented as mean ± SEM.

Results

Continuous measure of activity rhythms

All degus demonstrated an entrained and diurnal activity

pattern (Fig. 1). In the NP-acclimated group (Fig. 1a, c)

activity started with a peak just before ‘‘light-on’’ (08:00 h),

indicating that the animals were entrained to the NP

T. Ashkenazy-Frolinger et al.

123

schedule, and offset was entrained to ‘‘lights off’’ (20:00 h).

After the SP group was transferred to SP by advancing

lights offset, activity onset did not change [t(62) = 0.6,

p = 0.53], and activity offset began advancing toward the

new ‘‘lights off’’ time (Fig. 1b, c). At the end of the accli-

mation period, activity of the SP group ended significantly

earlier compared with the NP group [t(62) = 6.6,

p \ 0.0001]. As a result, total activity duration of the NP

group was 13.7 h while the duration of activity of the SP

degus decreased to 12.1 h per day (t(62) = 5.19,

p = 0.0001) and was not restricted to the light phase.

Weights

Animals maintained under NP conditions gained on aver-

age 8.7 g during the 6-week period of acclimatization and

experiment, whereas animals maintained under SP condi-

tions lost on average 8.5 g, but the difference between the

groups did not reach the level of statistical significance

(Fig. 2; t(12) = 1.77, p = 0.1).

Sweet solution preference

Degu-acclimated to NP gradually increased their sucrose

preference, while in the animals that were maintained

under SP conditions no such change was observed. The

difference between the groups became significant on days 4

and 5 (Fig. 3). Repeated-measures ANOVA across days,

Photoperiod effect: F(1, 12) = 1.68, p = 0.22. Day effect:

F(4, 48) = 1.12, p = 0.36. Photoperiod X Day interaction:

F(4, 48) = 2.62, p = 0.0466. Following comparisons for

separate days, photoperiod effect: day 1: t(12) = 0.69,

Fig. 1 Double daily plots of activity during the experiment. a Rep-

resentative actogram of an individual acclimated to 12-h:12-h NP.

b Representative actogram of an individual acclimated to 12-h:12-h

NP and transferred to 5:9 SP conditions on day 0. c Percentage of

daily activity during the last 5 days of the acclimation period to

12-h:12-h NP/5-h:19-h SP. (n = 8, mean ± SE). The NP group degus

were active during light hours with total activity duration of 13.7 h

with activity peaks occurring at the beginning and end of the dark

phase, while SP degu activity duration decreased to 12.1 h per day.

[t(62) = 5.19, p = 0.0001] and was not restricted to the light phase.

Activity onset of the SP animals did not change (c; t(62) = 0.6,

p = 0.53), but it ended earlier (c; t(62) = 6.6, p \ 0.0001). Black and

white bars at the top of the plot represent the light schedules in the

two treatments

Short photoperiod in diurnal degu

123

p = 0.5; day 2: t(12) = 0.59, p = 0.6; day 3: t(12) = 1.69,

p = 0.1; day 4: t(12) = 2.21, p = 0.046; day 5:

t(12) = 2.29, p = 0.04.

Light/dark box

Day length schedule had no effect on the time spent in the

light area of the box or on the number of entries to this area

(Table 1).

Open field

Photoperiod length did not affect distance travelled in the

open field (Table 1). However, animals from the SP group

spent 45 % less time than animals from the NP group in the

central area of the arena, suggesting an anxiety-like

behavior (Table 2; t(12) = 2.35, p = 0.037). Increased

anxiety-like behavior of the SP group in the open field is

also supported by additional measures: increased latency to

first entry into the central zone and increased time spent in

the corners of the arena (see Table 2 for data and statistics).

Forced swim test

A number of animals were excluded from the analysis in

the FST. Specifically, two animals from the NP group were

excluded because they escaped immediately before the test

and were captured only after some minutes. One animal

from the SP group was excluded because it demonstrated a

generalized sickness behavior in its cage after the first day

in the FST and therefore was not tested on the second day.

Hence, the final number of animals analyzed in the FST

was six for the NP group and five for the SP group. As

expected based on previous work with the fat sand rat, the

manipulation of photoperiod length had no effects on the

behavior on the first day of testing (Table 1); however,

despite the small number of animals, a near significant

difference between groups appeared on the second day of

1 2 3 4 50.00

0.25

0.50

0.75

1.00

NPSP

**

Day

Pre

fere

nce

rat

io

Fig. 3 Sucrose preference (mean ± SE) of neutral (NP, n = 8) and

short (SP, n = 6) photoperiod groups across the 5 days of testing.

Asterisk indicates a significant difference between groups (p \ 0.05).

Repeated-measures ANOVA across days, Photoperiod effect: F(1,

12) = 1.68, p = 0.22. Day effect: F(4, 48) = 1.12, p = 0.36. Pho-

toperiod X Day interaction: F(4, 48) = 2.62, p = 0.0466. Following

comparisons for separate days, photoperiod effect: day 1:

t(12) = 0.69, p = 0.5; day 2: t(12) = 0.59, p = 0.6; day 3:

t(12) = 1.69, p = 0.1; day 4: t(12) = 2.21, p = 0.046; day 5:

t(12) = 2.29, p = 0.04

Table 1 Some behavioral measures (mean ± SEM) not clearly

influenced by photoperiod length

Measure NP animals

(N = 8)

SP animals

(N = 6)

Statistics

Distance in a

large open

field (cm)

1,9103 ± 2,102 14,743 ± 2,067 t(12) = 1.44,

p = 0.17,

NS

Light/dark box,

time in light

part (s)

174 ± 14 150 ± 20 t(12) = 1.0,

p = 0.32,

NS

Light/dark box,

entries to light

part (#)

11.8 ± 2.0 12.3 ± 0.8 t(12) = 0.24,

p = 0.81,

NS

FST Day 1 (s to

sink)

Sink 1:

102.1 ± 23.1

Sink 1:

80.6 ± 21.6

t(9) = 0.67,

p = 0.52,

NS

Sink 2:

124.2 ± 27.3

Sink 2:

120.6 ± 13.1

t(9) = 0.11,

p = 0.91,

NS

Table 2 Effects of photoperiod manipulations on anxiety-related

measures (mean ± SEM) in the large open field

Measure NP animals

(N = 8)

SP animal

(N = 6)

Statistics

Time in center area

(s)

137.3 ± 21.6 75.0 ± 9.6 t(12) = 2.35,

p = 0.037

Latency to enter the

center area (s)

26.4 ± 3.6 80.6 ± 18.2 t(12) = 3.36,

p = 0.006

Time in corners (s) 515 ± 33 681 ± 38 t(11) = 3.3,

p = 0.007*

* One animal from the NP group was excluded from the analysis as

an outlier, being more than 2XSTD away from the mean

NP SP-20

-10

0

10

20

Wei

gh

t ch

ang

e (g

)

Fig. 2 Change in body weight (mean ± SE) in degus maintained

under neutral (NP, n = 8) or short (SP, n = 6) photoperiod condi-

tions during the 6-week experiment (weight at week 6-week at the

start of the behavioral tests). The different trends of the two groups

did not reach statistical significance t(12) = 1.77, p = 0.1

T. Ashkenazy-Frolinger et al.

123

testing with the SP group sinking approximately 30 %

faster than the NP animals (Fig. 4; time to second sink:

t(9) = 2.21, p = 0.054). Whereas the statistical analysis

shows only a near significant effect (p = 0.054), it is

suggested that with the small number of animals and the

expectation for faster sinking based on the previous results

in sand rats, the effects can be considered to reflect a real

difference.

Discussion

The results of the present study show that short photope-

riod conditions result in behavioral changes in the diurnal

degus that are generally similar to previous findings with

the diurnal fat sand rat and Nile grass rat and include

components of anxiety- and depression-like behavior.

Under both photoperiod schedules, at 20 �C and with no

running wheels available, all degus were diurnal and

entrained. These results are in accordance with their diur-

nal activity in their natural habitat as well as with findings

from other laboratories where degus are kept under similar

conditions (Kenagy et al. 2002b; Lee 2004; Kas and Edgar

1999; Goel and Lee 1995; Woods and Boraker 1975; Re-

finetti 1996). The degus were also previously reported to

show reduced activity during midday when ambient tem-

peratures are high or when kept under long photoperiods

(Kas and Edgar 1998; Kenagy et al. 2002a; Bacigalupe and

Rezende 2003; Kenagy and Vasquez 2004), which was also

evident in our results.

When transferred to SP conditions by advancing lights

offset, the degus significantly advanced their activity off-

set, but only by 1.6 h, resulting in activity continuing well

into the dark phase. These results are similar to ones

reported in the Nile grass rats, which did not respond

effectively to short photoperiod with respect to either the

duration of their active phase (Leach et al. 2013a; Refinetti

2004) or the elevated phase of PER1 and PER2 rhythms

within the SCN (Leach et al. 2013b).

We found that similar to previous work in diurnal

rodents, which demonstrated the development of anxiety-

and depression-like behavioral changes when maintained

under short photoperiod conditions (Einat et al. 2006;

Ashkenazy et al. 2009a, b; Ashkenazy-Frolinger et al.

2009; Leach et al. 2013a), degus maintained at 5-h:19-h

LD demonstrated anxiety-like behavior in the open field

test (Table 2; changes in measures related to the center of

the area), depression-like behavior in the sweet solution

preference (Fig. 3) and in the FST (Fig. 4), compared with

animals maintained under 12-h:12-h LD. It is important to

note that these behavioral changes are not the conse-

quences of a generalized reduction in activity, because no

effects of the photoperiod manipulation were shown in

locomotion levels in the large open field test (Table 1).

Despite the higher anxiety levels demonstrated by the

SP-acclimated animals in the open field test, such differ-

ences were not found in another test for anxiety-like

behavior, the light/dark box (Table 1). The lack of effect of

altered photoperiods in the light/dark box may indicate that

this test is unsuitable for diurnal animals. The main anxiety

provoking stimulus in this test is light. In nocturnal rodents,

light has a negative effect on activity levels and increases

anxiety and glucocorticoids levels (Barak and Kronfeld-

Schor 2013; Bilu and Kronfeld-Schor 2013; Cohen et al.

2010b; Eilam et al. 1999; Gutman et al. 2011; Hendrie

et al. 1996, 1998; Mandelik and Dayan 2000; Rotics et al.

2011). However, these effects are absent and sometime

opposite in diurnal rodents (Barak and Kronfeld-Schor

2013; Bilu and Kronfeld-Schor 2013; Cohen et al. 2010a;

Rotics et al. 2011). These findings are not different from

previous findings showing that diurnal Nile grass rats did

not show preference to the dark compartment of the light/

dark box (Ashkenazy-Frolinger et al. 2009). It is possible

that the elevated plus-maze, which is assumed to induce

anxiety because of the increased exposure of the animal in

the open compared to the closed arms, is a better test for

anxiety-like behavior in diurnal rodents. However, we were

unable to employ the elevated plus-maze test in the degu,

as in preliminary trials we found that the degu jumps off

the elevated maze easily and does so shortly after being

placed on it. Because degus live in rocky outcroppings and

steep bushy hills, it is not surprising that they are used to

jumping from heights.

In contrast with the clear effects of SP in diurnal rodents,

the effects of photoperiod manipulations on depression- and

anxiety-like responses in nocturnal animals is more com-

plicated and appears to depend on a number of factors. A

few studies report similar results to the ones presented in

Sink 1 Sink 20

50

100

150 NPSP

Sink

Tim

e to

sin

k (s

ec)

Fig. 4 The time to reach first and second sink in the FST of degus

acclimated to natural photoperiod. (NP, light gray bars n = 6) or

short photoperiod. (SP, dark gray bars, n = 5). Repeated-measures

AVOVA across tests: photoperiod effect: F(1, 9) = 3.15, p = 0.11,

test effect : F(1, 18) = 14.9, p = 0.004, test X photoperiod interac-

tion: F(1, 18) = 0.3, p = 0.59. Separate analysis for sink 1 and sink

2: sink 1: t(9) = 1.33, p = 0.2; sink 2 t(9) = 2.21, p = 0.054

Short photoperiod in diurnal degu

123

diurnal rodents: in Siberian hamsters, short photoperiod

(SP: 8L/16D) acclimation resulted in depressive-like

behavior in the sucrose preference test and the forced swim

(Pyter and Nelson 2006; Prendergast and Nelson 2005). The

same effects of SP were shown in Wistar rats acclimated to

an even milder SP (10L/14D) (Prendergast and Kay 2008),

but others found no such effect in more extreme SP (5-h:19-

h LD) (Molina hernandez and Tellez-Alcantara 2000), and

short photoperiod in rats was recently demonstrated to

increases sucrose consumption (Sinitskaya et al. 2008).

Similarly, in a study comparing the effects of long, short or

neutral photoperiods in two strains of mice (C57Bl/6 and

CD-1 mice), none of the manipulations resulted in a clear

depression- or anxiety-like behavioral phenotype (Flaisher-

Grinberg et al. 2011). The effects of different photoperiod

conditions in nocturnal animals may suggest that the

behavioral changes observed are not directly related to

specific photoperiod manipulations, but to a more general

effect possibly related to stress or to different evolutionary

background (Flaisher-Grinberg et al. 2011).

The changes that occur in the degu when maintained

under short photoperiod may be relevant to the underlying

mechanisms of depression. Whatever is responsible for the

inability of the degu to effectively adapt to the short pho-

toperiod may be part of the mechanism underlying the

development of depressive-like behavior under these con-

ditions. Altered circadian motor activity is an integral part

of the clinical symptoms of a depressive state (Todder et al.

2006). Changes in activity patterns were found in depres-

sed patients including reduced wake time activity levels

(Raoux et al. 1994), higher motor activity during sleep

(Volkers et al. 2003) and a more complex and less struc-

tured activity patterns (Berle et al. 2010; Hauge et al.

2011). Moreover, in SAD patients, the daily rhythms of

locomotor activity were found to be unstable, peaking at

different times across days (Teicher et al. 1997); they had

abnormal daily rhythms of temperature and melatonin

levels (Dahl et al. 1993; Avery et al. 1997).

Further support for the common mechanisms underlying

the response of diurnal rodents to short photoperiod and

depression is that similar to the effects in humans (Wehr

et al. 1986; Golden et al. 2005), bright light treatment

improved depression- and anxiety-like behaviors induced

by a short photoperiod regimen, while having no effects on

animals maintained in neutral photoperiods. Moreover,

similar to the effects in humans, application of morning

bright light was more effective than application of evening

bright light (Lewy et al. 1998; Ashkenazy et al. 2009a;

Krivisky et al. 2012). These results support the benefit of

bright light in the treatment of seasonal affective disorder

and offer new tool to study the underlying biological

mechanisms of this effect.

Taken together, the present study further supports the

utilization of diurnal rodents to model circadian rhythms-

related affective change. Beyond the possible diversity in

the mechanisms underlying diurnality in different animals,

there is now evidence that in three different diurnal species,

the fat sand rat, the grass Nile rat and the degu, shortening

of photoperiod results in the appearance of anxiety- and

depression-like behaviors. It is now possible to explore

common mechanisms of these changes and possibly gain

additional knowledge on the complex interactions between

circadian rhythms and affect.

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