Blunted accumbal dopamine response to cocaine following chronic social stress in female rats: exploring a link between depression and drug abuse

• Published in: Psychopharmacology Vol. 218; no. 1; pp. 271 - 279
• Main Authors: Shimamoto, Akiko, DeBold, Joseph F., Holly, Elizabeth N., Miczek, Klaus A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.11.2011; Springer; Springer Nature B.V
• Subjects: Animal models; Animals; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; Body Weight; Cocaine; Cocaine - administration & dosage; Cocaine - pharmacology; Depression; Depression - physiopathology; Depression, Mental; Disease Models, Animal; Dopamine; Dopamine - metabolism; Drug abuse; Drug therapy; Estrous Cycle; Estrus; Female; Females; Mental depression; Microdialysis; Neurons; Neurosciences; Neurotransmitters; Nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Nursing; Original Investigation; Pharmacology/Toxicology; Phenols; Psychiatry; Psychological aspects; Psychopharmacology; Rats; Rats, Long-Evans; Rodents; Saccharin; Saccharin - administration & dosage; Serotonin; Serotonin - metabolism; Sex Factors; Social interactions; Stress; Nucleus accumbens; Estrous cycles; Dopamine; Chronic social stress; Serotonin; Depression; Cocaine; Females
• DOI: 10.1007/s00213-011-2364-7
• ISSN: 0033-3158

Rationale Women have twice the risk as men to develop depression. Approximately, 24% of major depression disorder cases have comorbid disorders with substance abuse. Several central systems, including dopaminergic and serotonergic pathways, are thought to be involved in such comorbidity. Objectives The present study established a chronic social stress model in female rats, which produces some cardinal features of depressive-like symptoms. Further, we examined the effects of acute cocaine on dopamine (DA) and serotonin (5-HT) in the nucleus accumbens (NAc) using this model. Methods Female Long-Evans rats confronted a nursing dam in its home cage for 30 min twice daily for 21 days. The non-stressed control group was handled daily throughout the experiment. During the 21 days of stress, behaviors during confrontations, weight, preference for saccharin, and estrous cycles were measured. Ten days after the last confrontation, the experimental rat was challenged with 10 mg/kg of cocaine, and levels of DA and 5-HT in the NAc were measured using in vivo microdialysis. Results During the course of daily confrontations for 21 days, the experimental females significantly increased the duration of immobility, reduced weight gain and the preference for saccharin, and disrupted estrous cycles during the stress. Chronic social stress significantly attenuated cocaine-induced DA levels, and to some extent, attenuated a percent change of 5-HT compared to the non-stressed control group. Conclusions Chronic social defeat stress for 21 days induced physiological and behavioral depression-relevant deficits and blunted response of dopaminergic and to some extent, serotonergic neurons to cocaine challenge in females.