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

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Abstract

Rationale

Exposure to intermittent social defeat stress elicits corticotropin releasing factor (CRF) release into the VTA and induces long-term modulation of mesocorticolimbic dopamine activity in rats. These adaptations are associated with an intense cocaine-taking phenotype, which is prevented by CRF receptor antagonists.

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.

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.”

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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Acknowledgments

This work was funded by NIDA grant DA031734 to KAM.

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

    Michael Z. Leonard, Joseph F. DeBold & Klaus A. Miczek

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

    Klaus A. Miczek

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  1. Michael Z. Leonard
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Leonard, M.Z., DeBold, J.F. & Miczek, K.A. Escalated cocaine “binges” in rats: enduring effects of social defeat stress or intra-VTA CRF. Psychopharmacology 234, 2823–2836 (2017). https://doi.org/10.1007/s00213-017-4677-7

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