Modern Psychological Studies

Volume 21 Number 1 Article 12

2015

How social activity affects exercise in a rat model of depression proneness

Jacqueline Rojas Occidental College

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Recommended Citation Rojas, Jacqueline (2015) "How social activity affects exercise in a rat model of depression proneness," Modern Psychological Studies: Vol. 21 : No. 1 , Article 12. Available at: https://scholar.utc.edu/mps/vol21/iss1/12

This articles is brought to you for free and open access by the Journals, Magazines, and Newsletters at UTC Scholar. It has been accepted for inclusion in Modern Psychological Studies by an authorized editor of UTC Scholar. For more information, please contact [email protected]. HOW SOCIAL ACTIVITY AFFECTS EXERCISE 1 ROJAS

How Social Activity Affects Exercise in a Rat Model of Depression Proneness

Jacqueline Rojas

Occidental College

With depression rising worldwide, finding effective, affordable relief is a pressing global public health need. Social activity and physical activity both function as natural depression remedies, but depression can interfere with these activities. This study explores whether an increase in social activity can simultaneously increase voluntary exercise. If so, a single remedy could potentially yield two benefits. Rats were singly or paired housed to model social activity, and voluntary wheel running was measured. Depression proneness was modeled with Occidental Low-Saccharin- Consuming (LoS) rats; relative to high-saccharin-consuming (HiS) rats, LoS rats are more anxious and vulnerable to stress, both of which are risk factors for depression. Whether LoS rats would benefit more from social housing than HiS rats was of interest. Pair-housing increased wheel running, equally so among LoS and HiS rats. These results suggest that social activity may increase motivation to exercise, regardless of depression proneness. Keywords: paired housing, social activity, wheel running, physical activity, depression, rats

According to the World Health Organization, habituated significantly faster than non-exercised depression is one of the leading causes of death and animals (Sasse et al., 2008). This suggests that disability globally, with that number expected to repeated stress, a factor in developing depression, rise to the second leading cause by the year 2020 may be reduced by voluntary exercise. In a new (World Health Organization, 2012). With study of how exercise affects mood, individuals depression's capacity to cause great harm to those who self reported high tolerance to exercise who suffer from it, learning how to alleviate it experienced more positive affect and less negative becomes especially vital. Evidence-based treatment affect during a physiologically demanding task than strategies for depression range from medication to did their low tolerance peers(Tempest & Parfitt, more natural remedies, such as 30 minutes of 2015). This finding suggests that regular exercise exercise a day or social support from family and can facilitate mood regulation and thus help keep friends (Stanton & Reaburn, 2014; Steger & depression at bay. Kashdan, 2009). Many people diagnosed with However, one of the primary symptoms of depression look to natural remedies because they depression is the psychomotor agitation or are affordable and have fewer side effects than retardation. Many people suffering from Major prescription medication (Olfson et al., 2006; Depressive Disorder report reduced energy and Simon et al., 2004). However, methods used to activity (American Psychiatric Association, 2013), alleviate depression are rendered inadequate when making regular exercise simply out of the question. the symptoms of depression stop people from using The symptoms of depression that prevent people these methods. from exercising may also prevent them from One of the best-known and effective ways to seeking contact with loved ones. Thus, although a help treat mild to moderate depression without depressed person may crave social contact, medication is regular, vigorous exercise (Dunn et symptoms of depression lead to social isolation, al., 2005; Stanton & Reaburn, 2014). Exercise can which further reduces opportunities for physical be helpful for depression by facilitating the activity (American Psychiatric Association, 2013). habituation of corticosterone in response to stress; Identifying interventions that increase physical exercised animals that were exposed to stress activity could be a valuable way of disrupting the

MODERN PSYCHOLOGICAL STUDIES 88 HOW SOCIAL ACTIVITY AFFECTS EXERCISE I ROJAS vicious cycle. Increases in social activity, even with marker for stress vulnerability and associated just one person, might alleviate symptoms of emotional and energy regulatory processes. Since depression. This could in turn increase regular then, the HiS and LoS rats have been used to study exercise, producing a synergistic effect. If the relationship between emotion and how eating alleviating loneliness both improves mood and and physical activity are organized and regulated. increases spontaneous motor activity, it becomes a Selective pressure on the taste phenotypes was valuable direct and indirect intervention for expected to lead to differences in emotionality. depression. Potentially, then, we can "kill two birds Indeed, relative to high saccharin (HiS) rats, low with one stone" -- increasing social contact to not saccharin (LoS) rats are higher in anxiety and stress only alleviate feelings of social isolation but also to vulnerability, more sensitive to metabolic strengthen motivation to exercise. challenges, and lower in social status (Dess et al., Some practical and ethical limitations to 2013; Eaton et al., 2012). As predicted, the studying depression in humans can be overcome by distinctive HiS and LoS taste phenotypes serve as studying laboratory rats, whose nervous system and a marker for individual and social behaviors in these basic emotional systems are similar to humans' rats. These line differences are not a consequence of (Panksepp, 2005). Experimental (e.g. learned prior saccharin intake because in all studies, helplessness) and dispositional ("Flinders sensitive" including the present, the 24-hour two-bottle rats) rat models of depression have been validated assessment of the saccharin phenotype is conducted using behavioral and pharmacological methods after the experiment is over. The designations of (Overstreet, 2012). Moreover, exercise alleviates "LoS" and "HiS" then, are properly understood as depressive symptoms in rats (Zheng, 2005). terms referring to lineage — the behavior Studying laboratory rats therefore is a rigorous characteristic of parents, grandparents, and earlier experimental means of exploring whether social ancestors — and not to the saccharin intake of rats interventions alter spontaneous exercise. prior to other data collection in a particular study. The present study examined whether rats In the present study, the two lines were used to reunited with a sibling would exercise more than see whether the differences in taste phenotype rats that remain single housed. Motivation to would predict different effects of social housing on exercise was measured as wheel running. Wheel voluntary exercising. Because LoS rats are higher running can be seen as a measure of anxiety, in anxiety and stress vulnerability, we view LoS rats especially in experiments involving food scarcity as more similar to people who are depressed or are (Dess et al., 2007). However, wheel running prone to developing depression and would have induces positive affect and is positively reinforcing more to gain from the social housing. Therefore, in rats (Smith & Lynch, 2012), and even free-living we hypothesized that social housing would rodents wheel run when given the opportunity to differentially impact the two lines, with a robust do so (Meijer & Robbers, 2014). Thus, it is increase in running in the LoS line and relatively reasonable to assume that among the freely fed rats little impact on HiS rats. in the present study, wheel running was spontaneous and affectively positive. Method The present study also modeled individual differences in depression proneness with selectively Rats bred rats. Occidental HiS and LoS rats have been Adult experimentally naïve female rats (60- selectively bred for more than forty generations on 90 days old) from Generations 46 and 47 from the the basis of voluntary saccharin intake, a mixture of Occidental colony were used (HiS, n = 30; LoS, n artificial sweetener and water (Dess et al., 2013). = 30). Immediately prior to the experiment, they Selection on the taste phenotype was initiated as a were individually housed in stainless steel cages on result of several studies that revealed effects of a 12:12 light/dark cycle (0700-1900 light) with an experimental stress on ingestion, including reduced ambient temperature of 72 ± 4°F. Purina 5001 saccharin solution intake. Spontaneously low Rodent Chow and water were freely available. All saccharin intake was hypothesized to be a potential

MODERN PSYCHOLOGICAL STUDIES 89 HOW SOCIAL ACTIVITY AFFECTS EXERCISE I ROJAS procedures complied with a protocol approved by Running increased from Day 1 to Day 2. A 2x2 the Occidental College Institutional Animal Care mixed design ANOVA with line and day as and Use Committee. variables yielded a significant main effect of day, F(1,48) = 23.41, p < .001. No line effects were Apparatus significant. (See Figure 1.) Sessions occurred in stainless steel running Running and Bodyweight after Housing wheels equipped with a side cage, 350 mm in Assignment diameter (Model 86041; Lafayette Instruments, Lafayette IN). One running wheel was a different Increases from baseline running after rats Lafayette Instruments version of the model with were pair-housed (Pair) or were kept singly-housed the same diameter as the other wheels. (Single) are shown in Figure 2. Running continued to increase relative to baseline. As predicted, the Procedure running increases were larger in the pair-housed The experimental procedure was eight days rats. A 2x2x2 mixed design ANOVA with line, long (See Table 1). On four of those days, each rat housing condition, and day as variables revealed a was placed in an assigned running wheel for one significant housing condition x day interaction, p = .004. Bonferroni-adjusted hour. Rats were run in squads of six, always F(1,44) = 9.27, between 12:00 pm and 5:00 pm. After a squad of contrasts revealed a significant difference between six rats was placed in the running wheel, the days only in the Pair condition (p < .001). No experimenter left the room and closed the door; effects involving line were significant. Thus, automated counters monitored wheel running. contrary to our expectations, the effects of housing Running sessions were conducted on Days 1 were the same in HiS an LoS rats. and 2 of the experimental procedure. These The older running wheel yielded lower and sessions (Baseline 1 and Baseline 2) provided a more variable running and was excluded in the baseline measure of running during individual ANOVA above. Whether including it would have housing. After data collection on Day 2, all rats affected our conclusion was examined by repeating were re-housed. Thirty-two of the rats remained the ANOVA with data from that wheel included. singly-housed (Single condition) and the other rats The housing condition x day interaction remained = .011, as was the Day were reunited with a littermate (Pair condition). significant, F(1,56) = 6.83,p p < .001. Litters were balanced across experimental 3-Day 4 contrast in the Pair condition, Bodyweights on the final running day did conditions. Rats were left undisturbed for two days not differ significantly between lines (281.7 ± 4.0 g (Days 3 and 4) and then had a 1-hr running session on Day 5 (Test 1). They were again left for the LoS line, 267.5 ± 4.2 g for the HiS line). undisturbed for two days and had their final 1-hr Discussion running session on Day 8 (Test 2). Rats were weighed on Days 5 and 8 before the running As predicted, pair housing increased session. voluntary exercise. We expected that the LoS rats Rats were feed freely in their home cages. Food would be more sensitive to housing condition was unavailable only during running sessions (one because they are more prone to anxiety and hour on each of the four days). They were not food negative affect, mirroring people who have deprived. depression. However, LoS and HiS rats were equally sensitive to housing condition. To the Results extent that these findings generalize to people, we Baseline Bodyweight and Running can infer that socializing with loved ones might ameliorate depression due both to its direct, Initial bodyweights did not differ positive effects and indirectly due by increasing significantly between lines (M ± SEM, 278.8 ± 4.0 motivation to exercise. Studies on the effect of g for the LoS line, 265.5 ± 4.2 g for the HiS line). MODERN PSYCHOLOGICAL STUDIES 90 HOW SOCIAL ACTIVITY AFFECTS EXERCISE ROJAS

social activity on exercise in people would yield established neurohormonal mediators of stress and potentially beneficial results. mood, including dopamine, serotonin, and A limitation of this study with respect to glucocorticoids (Hammels et al., 2015; McEwen et human depression is the use of rats prone to al., 2015). At a higher level of organization, pair- depressive symptoms but in whom a depression- housing might have increased exercise due like syndrome (e.g. helplessness) had not been specifically to social interactions (play, contact, induced. Such a manipulation may reveal social etc.) or more generally by providing an enriched housing effects and differences between LoS and environment (Crofton, Zhang, & Green, 2015). In HiS rats that were not detected here. Nonetheless, their study of stress attenuation, Nyhuis et al. the present study lays a foundation for future (2010) examined whether non-specific enrichment research with rat depression models by providing a or in intervention-specific effect (in their case, time- and cost-effective procedure for generating a exercise) was responsible, and they concluded that reliable social housing effect. their effect was intervention specific. Nonetheless, A further limitation is that the effect of pair- in the present study, pair-housed rats may have housing was not distinguished from the effect of exercised more because pair housing provided an being reunited with a sibling. An assumption was enriched environment, and enrichment — and not that reunion with a sibling — a familiar rat — would social interaction specifically — increased running. make a rat less stressed than when paired with a rat A control study comparing pair-housed rats to who is a non-sibling — a stranger. This assumption singly-housed rats provided with an enriched was based partially on what would presumably environment, such as larger cages that have happen with humans; that is, being reunited with a compartments and tubes that a rat can use for close family member or loved one would be stimulation, would be informative as to the considered a stress reliever for people with mechanism of the group difference and thus its depression, more so than socializing with a potentially useful practical applications. stranger. However, family relationships can be emotionally complicated. To be sure that these References reunions are indeed stress-relieving, a follow-up American Psychiatric Association. (2013). Diagnostic and study could directly assess the behavioral or statistical manual of mental disorders (5th ed.). Arlington, VA: physiological effects of being reunited with the American Psychiatric Publishing. close kin. Crofton, EJ., Zhang, Y., & Green, T.A. (2015). Finally, this study was conducted once, with Inoculation stress hypothesis of environmental enrichment. a particular set of parameters. We chose to measure Neuroscience and Biobehavioral Reviews, 49, 19-31. Dess, N. K., Arnal, J., Chapman, C. D., Siebel, S., & acute rather than long-term effects of social VanderWeele, D. A. (2000). Exploring adaptations housing on exercise. Being pair-housed increased to famine: Rats selectively bred for differential intake on exercise over the course of a week, but it might or saccharin differ on deprivation-induced hyperactivity and might not continue to have an effect over the emotionality. International Journal of Comparative Psychology, course of weeks or months. Determining longer- 13, 34-52 Dess, N. K., Richard, J. M., Severe, S. F., & Chapman, term effects would be valuable, especially given that C. D. (2007). Temporal organization of eating in low- and exercise as a method of regulating depression is high- saccharin-consuming rats. International Journal of more useful both mentally and physically when Comparative Psychology, 20, 317-340. sustained. Also, wheel running was the measure of Dunn, A. L., Trivedi, M. H., Kampert, J. B., Clark, C. G., & Chambliss, H. 0. (2005). Exercise treatment for voluntary exercise, and it was measured for one depression: Efficacy and dose response. American journal of hour on four days over an 8-day course. Whether a Preventive Medicine, 28(1), 1-8. different measure or duration of exercise would Eaton, J. M., Dess, N. K., & Chapman, C. D. (2012). yield the same results remains to be determined. Sweet success, bitter defeat: A taste phenotype predicts social status in selectively bred rats. PLOS One, 7(10):e46606. An important future direction for research Greenwood, B. N., & Fleshner, M. (2008). Exercise, concerns the mechanisms of the effect of pair learned helplessness, and the stress-resistant brain. housing reported here. One fruitful direction is Neuromolecular Medicine, 10, 81-98. examination of effects of pair-housing on well

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Hammels, C., Pishva, E., De Vry, J., van den Hove, Smith, M. A., & Lynch, W. J. (2012). Exercise as a D.L.A., Prickaerts, J., et al. (2015). Defeat stress in rodents: potential treatment for drug abuse: Evidence from preclinical From behavior to molecules. Neuroscience and Biobehavioral studies. Frontiers in Psychiatry, 2. Reviews, 59, 111-140. Stanton, R., & Reaburn, P. (2014). Exercise and the McEwen, B.S., Bowles, N.P., Gray, J.D., Hill, M.N., treatment of depression: A review of the exercise program Hunter, R.G., et al. (2015). Mechanisms of stress in the brain. variables. Journal of Science and Medicine in Sport, 17(2), 177- Nature Neuroscience, 18, 1353-1363. 82. Meijer, J. H., & Robbers, Y. (2014). Wheel running in Steger, M. F., & Kashdan, T. B. (2009). Depression and the wild. Proceedings of the Royal Society B: Biological Sciences, everyday social activity, belonging, and well-being. Journal of 281(1786), 20140210. Counseling Psychology, 56(2), 289-300. Nyhuis, T.J., Masini, C.V., Sasse, S.K., Day, H. E.W., Tempest, G. & Parfitt, G. (2015). Self-reported & Campeau, S. (2010). Physical activity, but not tolerance influences prefrontal cortex hemodynamics and environmental complexity, facilitates HPA axis response affective responses. Cognitive, Affective, & Behavioral habituation to repeated audiogenic stress despite neurotrophin Nueroscience, 16, 63-71. mRNA regulation in both conditions. Brain Reseach, 1362, 68- World Health Organization. (2012). Diabetes (Fact 77. sheet No. 369). Retrieved from Olfson, M., Blanco, C., Liu, L., Moreno, C., & Laje, G. http://www.who.int/mediacentre/factsheets/fs369/en/ (2006). National trends in outpatient psychotherapy. American Zheng, H. (2005). Beneficial effects of exercise and its Journal of Psychiatry, 167, 1456-1463. molecular mechanisms on depression in rats. Behavioral Brain Overstreet, D. H. (2012). Modeling depression in animal Research, 168, 47-55. models. Methods in Molecular Biology, 829,125-44. Panksepp, J. (2005). On the embodied neural nature of core emotional affects. Journal of Consciousness Studies, 12(8- Author Note 10), 158-184. Sasse, S.K., Greenwood, B.N., Masini, C.V., Nyhuis, The author declares no conflicts of interest. T.J., Fleshner, M., Day, H.E., Campeau, S. (2008). Chronic voluntary wheel running facilitates corticosterone response The support of a Mary S. Caswell Endowment habituation to repeated audiogenic stress exposure in male rats. Summer Research Fellowship is gratefully Stress, 11, 425-437. acknowledged. Simon, G. E., Fleck, M., Lucas, R., & Bushnell, D. M. The author thanks Dr. Nancy K. Dess and (2004). Prevalence and predictors of depression treatment in Dr. Clinton D. Chapman for their assistance and an international primary care study. American Journal of Psychiatry, 161(9), 1626-1634. support throughout the project.

Appendix Table 1 Procedural Schedule Day 1 Day 2 Day 3 Day 4 Days Day 6 Day? Day 8 Baseline 1 Baseline 2 Test 1 Test 2 One hour in One hour in One hour in One hour in wheel wheel wheel wheel Note. The above table describes the procedural schedule for each squad of rats.

MODERN PSYCHOLOGICAL STUDIES 92 HOW SOCIAL ACTIVITY AFFECTS EXERCISE I ROJAS

Figure 1. Mean wheel revolutions (± SEM) in LoS and the HiS rats on baseline running days.

140

) e 120 hang

C 100 ( 80 ions t

lu 60 vo

l Re 40

hee 20 W

Test 1 Test 2 Test 1 Test 2 Test 1 Test 2 Test 1 Test 2 LoS Single LoS Pair HiS Single HiS Pair

Figure 2. Mean running increases from baseline (± SEM) for each group on Test 1 and Test 2.

MODERN PSYCHOLOGICAL STUDIES 93