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


CONCLUSIONS
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.
Anker
Justin J
JJ
Department of Psychiatry, University of Minnesota, MMC 392, Minneapolis, MN 55455, USA. anke0022@umn.edu
Zlebnik
Natalie E
NE
Carroll
Marilyn E
ME
D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D011280:Pregnanolone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage*; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D013395:Sucrose; D011280:Pregnanolone; D003042:Cocaine