Skip to main content

Advertisement

SpringerLink
Log in

Individual differences in anhedonic and accumbal dopamine responses to chronic social stress and their link to cocaine self-administration in female rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Women are twice as likely as men to develop major depressive disorder. Exposure to chronic stress can induce depression in some vulnerable individuals, while others are resistant to depressive-like symptoms after equivalent levels of chronic stress.

Objectives

In female rats, individual differences in saccharin intake during chronic social defeat stress may predict subsequent cocaine self-administration, and may be attributed to alterations in mesolimbic dopamine activity.

Methods

Female rats were exposed to 21 days of chronic social defeat stress, during which they were evaluated for their anhedonia-like responses in the form of saccharin intake. After chronic social defeat stress, the rats were tested for behavioral cross-sensitization to cocaine and escalated cocaine self-administration in a 24-h “binge.” A separate group of animals underwent in vivo microdialysis of the nucleus accumbens (NAc) shell to assess dopamine (DA) in response to acute cocaine challenge.

Results

Cluster analysis revealed two phenotypes among the stressed female rats based on their saccharin intake while being exposed to stress, termed stress-resistant (SR, 28 %) and stress-sensitive (SS, 72 %). The amount of cocaine self-administered during the 24-h “binge” was positively correlated with preceding saccharin intake. The NAc DA response to a cocaine challenge was significantly lower in SR rats than in the SS and non-stressed control rats. No other significant differences were observed in behavioral cross-sensitization or cocaine self-administration prior to the “binge.”

Conclusion

Female rats showed individual differences in their anhedonic-like response to chronic social defeat stress, and these differences were reliably associated with subsequent cocaine-taking behavior.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th Edition: DSM-5. American Psychiatric Publishing, Arlington, VA

    Book  Google Scholar 

  • Anisman H, Lacosta S, Kent P, McIntyre DC, Merali Z (1998) Stressor-induced corticotropin-releasing hormone, bombesin, ACTH and corticosterone variations in strains of mice differentially responsive to stressors. Stress 2:209–220

    Article  CAS  PubMed  Google Scholar 

  • Anisman H, Zacharko RM (1992) Depression as a consequence of inadequate neurochemical adaptation in response to stressors. Br J Psychiatry Suppl36-43

  • Bergstrom A, Jayatissa MN, Mork A, Wiborg O (2008) Stress sensitivity and resilience in the chronic mild stress rat model of depression; an in situ hybridization study. Brain Res 1196:41–52

    Article  CAS  PubMed  Google Scholar 

  • Berton O, Covington HE III, Ebner K, Tsankova NM, Carle TL, Ulery P, Bhonsle A, Barrot M, Krishnan V, Singewald GM, Singewald N, Birnbaum S, Neve RL, Nestler EJ (2007) Induction of [delta]fosb in the periaqueductal gray by stress promotes active coping responses. Neuron 55:289–300

    Article  CAS  PubMed  Google Scholar 

  • Berube P, Laforest S, Bhatnagar S, Drolet G (2013) Enkephalin and dynorphin mRNA expression are associated with resilience or vulnerability to chronic social defeat stress. Physiol Behav 122:237–245

    Article  CAS  PubMed  Google Scholar 

  • Blumner KH, Marcus SC (2009) Changing perceptions of depression: ten-year trends from the general social survey. Psychiatr Serv 60:306–312

    Article  PubMed  Google Scholar 

  • Bracke P (2000) The three-year persistence of depressive symptoms in men and women. Soc Sci Med 51:51–64

    Article  CAS  PubMed  Google Scholar 

  • Carroll ME, Morgan AD, Lynch WJ, Campbell UC, Dess NK (2002) Intravenous cocaine and heroin self-administration in rats selectively bred for differential saccharin intake: phenotype and sex differences. Psychopharmacology (Berlin) 161:304–313

    Article  CAS  Google Scholar 

  • Chrousos GP (2000) Stress, chronic inflammation, and emotional and physical well-being: concurrent effects and chronic sequelae. J Allergy Clin Immunol 106:S275–S291

    Article  CAS  PubMed  Google Scholar 

  • Covington HE III, Miczek KA (2001) Repeated social-defeat stress, cocaine or morphine. Effects on behavioral sensitization and intravenous cocaine self-administration “binges”. Psychopharmacology (Berl) 158:388–398

    Article  CAS  Google Scholar 

  • Dalla C, Pitychoutis PM, Kokras N, Papadopoulou-Daifoti Z (2010) Sex differences in animal models of depression and antidepressant response. Basic Clin Pharmacol Toxicol 106:226–233

    Article  CAS  PubMed  Google Scholar 

  • Der-Avakian A, Mazei-Robison MS, Kesby JP, Nestler EJ, Markou A (2014) Enduring deficits in brain reward function after chronic social defeat in rats: susceptibility, resilience, and antidepressant response. Psychiatry, Biol

    Google Scholar 

  • Friedman AK, Walsh JJ, Juarez B, Ku SM, Chaudhury D, Wang J, Li X, Dietz DM, Pan N, Vialou VF, Neve RL, Yue Z, Han MH (2014) Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience. Science 344:313–319

    Article  CAS  PubMed  Google Scholar 

  • Grippo AJ, Moffitt JA, Johnson AK (2002) Cardiovascular alterations and autonomic imbalance in an experimental model of depression. Am J Physiol Regul Integr Comp Physiol 282:R1333–R1341

    CAS  PubMed  Google Scholar 

  • Handa RJ, Burgess LH, Kerr JE, O’Keefe JA (1994) Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis. Horm Behav 28:464–476

    Article  CAS  PubMed  Google Scholar 

  • Holly EN, Shimamoto A, DeBold JF, Miczek KA (2012) Sex differences in behavioral and neural cross-sensitization and escalated cocaine taking as a result of episodic social defeat stress in rats. Psychopharmacology (Berl) 224:179–188

    Article  CAS  Google Scholar 

  • Holsboer F (1995) Neuroendocrinology of mood disorders. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology-4th Generation of Progress. Raven, New York

    Google Scholar 

  • Kabbaj M, Norton CS, Kollack-Walker S, Watson SJ, Robinson TE, Akil H (2001) Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior. Psychopharmacology (Berl) 158:382–387

    Article  CAS  Google Scholar 

  • Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289:3095–3105

    Article  PubMed  Google Scholar 

  • Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:617–627

    Article  PubMed Central  PubMed  Google Scholar 

  • Koob GF (2008) A role for brain stress systems in addiction. Neuron 59:11–34

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, Laplant Q, Graham A, Lutter M, Lagace DC, Ghose S, Reister R, Tannous P, Green TA, Neve RL, Chakravarty S, Kumar A, Eisch AJ, Self DW, Lee FS, Tamminga CA, Cooper DC, Gershenfeld HK, Nestler EJ (2007) Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131:391–404

    Article  CAS  PubMed  Google Scholar 

  • Lecca D, Cacciapaglia F, Valentini V, Acquas E, Di CG (2007) Differential neurochemical and behavioral adaptation to cocaine after response contingent and noncontingent exposure in the rat. Psychopharmacology (Berl) 191:653–667

    Article  CAS  Google Scholar 

  • Lin SJ, Epps SA, West CH, Boss-Williams KA, Weiss JM, Weinshenker D (2012) Operant psychostimulant self-administration in a rat model of depression. Pharmacol Biochem Behav 103:380–385

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lonstein JS, Gammie SC (2002) Sensory, hormonal, and neural control of maternal aggression in laboratory rodents. Neurosci Biobehav Rev 26:869–888

    Article  PubMed  Google Scholar 

  • McEwen BS, Stellar E (1993) Stress and the individual: mechanisms leading to disease. Arch Intern Med 153:2093–2101

    Article  CAS  PubMed  Google Scholar 

  • Miczek KA, Nikulina EM, Shimamoto A, Covington HE III (2011) Escalated or suppressed cocaine reward, tegmental BDNF and accumbal dopamine due to episodic vs. continuous social stress in rats. J Neurosci 31:9848–9857

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mutschler NH, Covington HE 3rd, Miczek KA (2001) Repeated self-administered cocaine “binges” in rats: effects on cocaine intake and withdrawal. Psychopharmacology (Berl) 154:292–300

  • National Research Council (2011) Guide for the care and use of laboratory animals: eighth edition. National Academy Press, Washington DC

    Google Scholar 

  • Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, 3rd edn. Academic, San Diego

  • Pettinati HM, O’Brien CP, Dundon WD (2013) Current status of co-occurring mood and substance use disorders: a new therapeutic target. Am J Psychiatry 170:23–30

    Article  PubMed Central  PubMed  Google Scholar 

  • Richardson NR, Roberts DC (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66:1–11

  • Roth-Deri I, Friedman A, Abraham L, Lax E, Flaumenhaft Y, Dikshtein Y, Yadid G (2009) Antidepressant treatment facilitates dopamine release and drug seeking behavior in a genetic animal model of depression. Eur J Neurosci 30:485–492

    Article  PubMed  Google Scholar 

  • Rygula R, Abumaria N, Domenici E, Hiemke C, Fuchs E (2006) Effects of fluoxetine on behavioral deficits evoked by chronic social stress in rats. Behav Brain Res 174:188–192

    Article  CAS  PubMed  Google Scholar 

  • Rygula R, Abumaria N, Flügge G, Fuchs E, Ruther E, Havemann-Reinecke U (2005) Anhedonia and motivational deficits in rats: impact of chronic social stress. Behav Brain Res 162:127–134

    Article  PubMed  Google Scholar 

  • Rygula R, Abumaria N, Havemann-Reinecke U, Ruther E, Hiemke C, Zernig G, Fuchs E, Flügge G (2008) Pharmacological validation of a chronic social stress model of depression in rats: effects of reboxetine, haloperidol and diazepam. Behav Pharmacol 19:183–196

    Article  CAS  PubMed  Google Scholar 

  • Shimamoto A, DeBold JF, Holly EN, Miczek KA (2011) Blunted accumbal dopamine response to cocaine following chronic social stress in female rats: exploring a link between depression and drug abuse. Psychopharmacology (Berl) 218:271–279

    Article  CAS  Google Scholar 

  • Staples RE, Geils HD (1965) An observation of the vaginal smear of the rat. J Endocrinol 32:263–264

    Article  CAS  PubMed  Google Scholar 

  • Substance Abuse and Mental Health Services Administration (2010) Results from the 2009 National Survey on Drug Use and Health: volume I. Summary of National Findings. US Department of Health and Human Services, Rockville

    Google Scholar 

  • Wilkinson MB, Xiao G, Kumar A, Laplant Q, Renthal W, Sikder D, Kodadek TJ, Nestler EJ (2009) Imipramine treatment and resiliency exhibit similar chromatin regulation in the mouse nucleus accumbens in depression models. J Neurosci 29:7820–7832

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Willner P, Benton D, Brown E, Cheeta S, Davies G, Morgan J, Morgan M (1998) “Depression” increases “craving” for sweet rewards in animal and human models of depression and craving. Psychopharmacology (Berl) 136:272–283

    Article  CAS  Google Scholar 

  • Willuhn I, Burgeno LM, Groblewski PA, Phillips PE (2014) Excessive cocaine use results from decreased phasic dopamine signaling in the striatum. Nat Neurosci 17:704–709

    Article  CAS  PubMed  Google Scholar 

  • Wood RI (2010) The many facets of sex and drugs. Horm Behav 58:1

    Article  PubMed  Google Scholar 

  • Wood SK, Walker HE, Valentino RJ, Bhatnagar S (2010) Individual differences in reactivity to social stress predict susceptibility and resilience to a depressive phenotype: role of corticotropin-releasing factor. Endocrinology 151:1795–1805

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zurawek D, Faron-Gorecka A, Kusmider M, Kolasa M, Gruca P, Papp M, Dziedzicka-Wasylewska M (2013) Mesolimbic dopamine D(2) receptor plasticity contributes to stress resilience in rats subjected to chronic mild stress. Psychopharmacology (Berl) 227:583–593

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by a National Institute on Drug Abuse Grant to KAM (DA031734) and a National Institute on Alcohol Abuse and Alcoholism Grant to KAM (AA013983). We appreciate the contribution of Mr. Durwood Marshall from Tufts University Technology Services for assisting with the cluster analysis. We also thank Mr. Tom Sopko for helping to prepare the manuscript.

Author information

Authors and Affiliations

  1. Department of Psychology, Tufts University, Medford, MA, USA

    Akiko Shimamoto, Elizabeth N. Holly, Christopher O. Boyson, Joseph F. DeBold & Klaus A. Miczek

  2. Department of Neuroscience, Tufts University, Boston, MA, USA

    Klaus A. Miczek

  3. Department of Neuroscience and Pharmacology, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Blvd., Nashville, TN, USA

    Akiko Shimamoto

Authors
  1. Akiko Shimamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth N. Holly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher O. Boyson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joseph F. DeBold
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Klaus A. Miczek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akiko Shimamoto.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shimamoto, A., Holly, E.N., Boyson, C.O. et al. Individual differences in anhedonic and accumbal dopamine responses to chronic social stress and their link to cocaine self-administration in female rats. Psychopharmacology 232, 825–834 (2015). https://doi.org/10.1007/s00213-014-3725-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-014-3725-9

Keywords

Search

Navigation