Progesterone metabolite allopregnanolone attenuates the reinstatement of cocaine‐seeking behavior in female not male rats

Abstract

Previous research indicates that progesterone decreased cocaine‐seeking in female rats. The attenuating effects of progesterone may be, in part, due to its metabolite, allopregnanolone (ALLO). ALLO, is a neurosteroid that is also a positive modulator of GABA A receptors. ALLO has been shown to decrease the sensitizing effects of cocaine and reduce lethality associated with cocaine overdose in mice. The purpose of the present study was to examine the effects of ALLO on the reinstatement of cocaine‐seeking in female and male rats. Rats were trained to lever press for i.v. infusions of cocaine during 2‐hour sessions. Once acquisition criteria were met, they continued cocaine self‐administration for 14 days. Cocaine was then replaced with saline, and lever‐pressing was allowed to extinguish over 21 days. After the extinction phase rats received ALLO (15 mg/kg or 30 mg/kg) or vehicle pretreatment 30 min prior to the session for 3 days. Rats were then tested during reinstatement with 3 randomly administered doses of cocaine (5, 10 and 15 mg/kg, i.p.), each separated by one day of saline treatment. The results of the study indicate that ALLO, administered to females at the 15 and 30 mg/kg dose, decreased cocaine‐seeking. However, ALLO did not effect cocaine‐seeking behavior in male rats. These findings suggest that ALLO may provide a novel approach for preventing relapse in female cocaine‐abusers.