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

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.