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Differential effects of allopregnanolone on the escalation of cocaine self-administration and sucrose intake in female rats

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Abstract

Rationale

Evidence suggests that the progesterone metabolite allopregnanolone (ALLO) decreases cocaine seeking in animal models of relapse.

Objective

The purpose of this study was to examine the effects of ALLO on an animal model of cocaine and sucrose bingeing (escalation). Allopregnanolone's effects on yohimbine-induced sucrose intake were also examined. In a separate group of animals, dose interactions between ALLO and cocaine were examined with an abbreviated procedure, a short access progressive ratio (PR) schedule for cocaine reinforcement.

Methods

Female rats were treated with ALLO (15 mg/kg, s.c.) or vehicle (VEH) and trained to lever press for cocaine infusions (0.4 mg/kg) under an extended-access procedure. In a separate condition, other ALLO- and VEH-treated female rats self-administered orally delivered liquid sucrose. Allopregnanolone and VEH treatment was then discountinued and the sucrose-maintained rats were administered priming injections of saline, yohimbine, or yohimbine + ALLO. For the PR condition, rats were first treated with VEH until reaching stability at four doses of cocaine (0.2, 0.4, 0.8, and 1.6 mg/kg in mixed order). Subsequently, rats re-established their baseline cocaine intake at the four cocaine doses following treatment with each of two counterbalanced doses of ALLO (15 and 30 mg/kg).

Results

ALLO significantly blocked the escalation of cocaine self-administration but did not reliably affect intake of sucrose under a similar condition or affect cocaine intake at several doses under a PR schedule. Yohimbine significantly increased sucrose intake while ALLO failed to attenuate this increase.

Conclusion

These findings indicate that ALLO protects against binge-like patterns of cocaine intake but does not reduce sugar intake that is acutely increased by yohimbine in females.

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Acknowledgements

This research was supported by the National Institute on Drug Abuse grants, R01 DA 003240-26, R01 DA019942-3, K05 015267-08 (MEC), and F31 DA 023301-02 (JJA). The authors would like to thank Luke Gliddon, Nathan Holtz, Emily Kidd, Brandon Knight, Kinner Patel, Paul Regier, Amy Saykao, Matthew Starr, Rachael Turner, Troy Velie, and Jeremy Williams for their technical assistance.

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  1. Department of Psychiatry, University of Minnesota, MMC 392, Minneapolis, MN, 55455, USA

    Justin J. Anker, Natalie E. Zlebnik & Marilyn E. Carroll

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  1. Justin J. Anker
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Correspondence to Justin J. Anker.

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Anker, J.J., Zlebnik, N.E. & Carroll, M.E. Differential effects of allopregnanolone on the escalation of cocaine self-administration and sucrose intake in female rats. Psychopharmacology 212, 419–429 (2010). https://doi.org/10.1007/s00213-010-1968-7

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