Escalated cocaine "binges" in rats: enduring effects of social defeat stress or intra-VTA CRF

大鼠可卡因“狂饮”升级:社交失败压力或腹侧被盖区内 CRF 的持久影响

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作者:Michael Z Leonard, Joseph F DeBold, Klaus A Miczek

Conclusions

Repeated infusion of CRF into the VTA persistently alters cocaine valuation and intensifies binge-like drug intake in a CRF-R1-dependent manner. Conversely, the persistent pattern of cocaine bingeing induced by social defeat stress may suggest impaired inhibitory control, independent of reward valuation.

Methods

Male Long-Evans rats were microinjected into the VTA with CRF (50 or 500 ng/side), vehicle, or subjected to social defeat stress, intermittently over 10 days. Animals were then trained to self-administer IV cocaine (FR5). Economic demand for cocaine was evaluated using a within-session behavioral-economics threshold procedure, which was followed by a 24-h extended access "binge."

Objective

The present studies examine whether infusion of CRF into the VTA is sufficient to escalate cocaine-taking behavior, in the absence of social defeat experience. Additionally, we aimed to characterize changes in cocaine valuation that may promote binge-like cocaine intake.

Results

Rats that experienced social defeat or received intra-VTA CRF microinfusions (50 ng) both took significantly more cocaine than controls over the 24-h binge but showed distinct patterns of intake. Behavioral economic analysis revealed that individual demand for cocaine strongly predicts binge-like consumption, and demand elasticity (i.e. α) is augmented by intra-VTA CRF, but not by social defeat. The effects of CRF on cocaine-taking were also prevented by intra-VTA pretreatment with CP376395, but not Astressin-2B. Conclusions: Repeated infusion of CRF into the VTA persistently alters cocaine valuation and intensifies binge-like drug intake in a CRF-R1-dependent manner. Conversely, the persistent pattern of cocaine bingeing induced by social defeat stress may suggest impaired inhibitory control, independent of reward valuation.

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