Effects of progesterone on the reinstatement of cocaine-seeking behavior in female rats.

Abstract

Estradiol benzoate (EB) facilitates the acquisition and reinstatement of cocaine-seeking behavior when administered to ovariectomized (OVX) rats. In contrast, progesterone (P) decreases acquisition of cocaine self-administration, but the effects of P on the reinstatement of drug seeking are not known. The purpose of the present study was to compare the effects of EB and P on the reinstatement of cocaine-seeking behavior in female rats. Rats received either OVX or sham surgery (SH) and were trained to lever press for intravenous cocaine infusions (0.4 mg/kg) under a fixed ratio 1, 20-s time-out schedule during daily 2-hr sessions. After 14 days of stable responding, saline replaced cocaine, and a 21-day extinction period began. After extinction, rats were separated into 5 treatment groups (OVX+EB, OVX+EB+P, OVX+vehicle [VEH], SH+P, or SH+VEH), and VEH, EB, or EB+P was administered 30 min prior to each session for 5 days. After 3 days of hormone treatment, rats received a saline or cocaine (10 mg/kg) injection, and reinstatement of lever responding was assessed. Reinstatement responding in the OVX+EB group was greater relative to the OVX+EB+P, SH+P, and OVX+VEH groups, which had low levels of cocaine-primed responding. The SH+VEH and OVX+EB groups displayed similar high levels of cocaine-elicited reinstatement. The suppression of cocaine-induced reinstatement following P treatment suggests a role for P in the prevention of relapse to cocaine self-administration in female cocaine users.

Increasing Progesterone Levels Are Associated With Smoking Abstinence Among Free-Cycling Women Smokers Who Receive Brief Pharmacotherapy

“…Although this interpretation is somewhat complicated because a rise in estradiol also occurs in the luteal phase, there is preclinical research with ovariectomized rats showing that exogenous progesterone administration can undo the liabilities posed by exogenous estradiol. [58][59][60][61] This line of research suggests that when both hormones are present, it is likely the case that progesterone dominates.…”

A Cocaine Hydrolase Engineered from Human Butyrylcholinesterase Selectively Blocks Cocaine Toxicity and Reinstatement of Drug Seeking in Rats

“…Overdose rescue and relapse suppression by cocaine hydrolase S Brimijoin et al , estrogen status (Anker et al, 2007;Larson et al, 2005), higher drug dose (Carroll and Campbell, 2000), addiction-prone phenotypes such as impulsivity (Perry et al, 2005) or sweet-preference (Perry et al, 2006), and food restriction (Comer et al, 1995). Especially powerful are 'priming exposures' of drugs with related pharmacological mechanisms (Carroll and Comer, 1996;Carroll and Campbell, 2000;Shalev et al, 2002;Shaham et al, 2003).…”

Effects of allopregnanolone on the reinstatement of cocaine-seeking behavior in male and female rats

“…For example, women reported increased amphetamine- (Justice and de Wit 1999;White et al 2002) and cocaineelicited (Evans et al 2002;Sofuoglu et al 1999) positive subjective ratings during the follicular phase of the menstrual cycle when circulating estrogen levels are high, compared to the luteal phase when estrogen levels are lower. Similarly, in preclinical research, the administration of estrogen enhanced the acquisition (Lynch et al 2001;Hu et al 2004;Jackson et al 2006), escalation , and reinstatement Anker et al 2007) of cocaine-seeking behavior. In contrast, clinical and preclinical research suggests that PROG inhibits cocaine-elicited effects in females.…”