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

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.

Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice

“…Additionally, our results showed that adolescent MSEW group of mice reduced the consumption of saccharin, suggesting that early life neglect induced responses related to anhedonia, a core symptom of depressive states that could be observed in rodents after the exposure to a chronic stress (D'Aquila et al, 1997;Harkin et al, 2002;Strekalova et al, 2004), like the MSEW procedure. Our results agree well with previous data showing a reduced in the saccharin consumption in two accepted model to induce a depressive-like state in rodents as chronic mild stress (Harkin et al, 2002;Pijlman et al, 2003;Schweizer et al, 2009), and social defeat (Furay et al, 2011;Shimamoto et al, 2015).…”

Capturing Individual Differences: Challenges in Animal Models of Posttraumatic Stress Disorder and Drug Abuse

“…Similarly, we have recently reported individual differences in anhedonic-like responses following chronic social defeat stress in female rats (9). Female rats were characterized as either ‘stress-vulnerable’ or ‘stress-resistant’ based upon saccharin preference during chronic social defeat, and only one subgroup showed increased cocaine self-administration during a 24 h “binge”, as well as suppressed cocaine-induced extracellular dopamine efflux in the nucleus accumbens shell.…”

Stress, sex, and motivated behaviors

“…Social defeat in California mice has been optimized so that on average males and females are exposed to the same number of aggressive interactions across three episodes of defeat (Trainor et al , 2013). Lactating rat dams are used to induce defeat in female rats (Holly et al , 2012; Shimamoto et al , 2015). Although aggression levels of males and lactating dams are typically not compared in the same study, long lasting behavioral changes are induced (Holly et al , 2012; Shimamoto et al , 2015).…”

“…Lactating rat dams are used to induce defeat in female rats (Holly et al , 2012; Shimamoto et al , 2015). Although aggression levels of males and lactating dams are typically not compared in the same study, long lasting behavioral changes are induced (Holly et al , 2012; Shimamoto et al , 2015). Interestingly, female Syrian hamsters are more aggressive than males (Payne & Swanson, 1970), which has facilitated studies of defeat stress in female hamsters.…”