Potentiation of cocaine-primed reinstatement of drug seeking in female rats during estrus

Abstract

Estrus females display heightened sensitivity to the motivational and/or stimulant effects of cocaine, suggesting that hormonal state modulates drug craving and propensity for drug relapse in cocaine addicts.

Estrogen Receptor β, but not α, Mediates Estrogen's Effect on Cocaine-Induced Reinstatement of Extinguished Cocaine-Seeking Behavior in Ovariectomized Female Rats

“…Given the results of the present study, it is unlikely that the effects of estrogen on reinstatement are a result of ERb activation in the amygdala, as this region has been implicated in reinstatement of drug-seeking behavior induced by cocaine-associated cues, but not for reinstatement elicited by priming injections of cocaine (McFarland and Kalivas, 2001;Kalivas and McFarland, 2003;Bossert et al, 2005). This idea is supported by recent studies in rats indicating that gonadal hormones (eg, estrogen) influence reinstatement induced by cocaine (Kippin et al, 2005;, but not reinstatement elicited by exposure to cocaine-associated cues . Given that cocaine-induced reinstatement involves more direct activation of the mesolimbic pathway (ie, VTA to nucleus accumbens), it is likely that estrogen may be acting on receptors in these areas.…”

“…It has been reported that females are more responsive than males to stimuli that cause relapse, including exposure to stress (Klein et al, 1997), drugs (Lynch and Carroll, 2000;Kippin et al, 2005), and drugassociated cues (Robbins et al, 1999;Elman et al, 2001, but see also Avants et al, 1995;Fuchs et al, 2005). Research on sex differences in the behavioral and neurochemical responses to drugs, particularly the stimulant drugs cocaine and amphetamine/methamphetamine, indicates that the gonadal hormone estrogen may be responsible for the enhanced drug-induced responses in females compared to males (for review, see Becker, 1999;Festa and Quiñones-Jenab, 2004).…”

“…Although several studies have examined estrogenmediated effects on cocaine-mediated responses (Lynch et al, 2002;Festa and Quiñones-Jenab, 2004;Roth et al, 2004), including the reinstatement of cocaine-seeking behavior after an abstinence period Kippin et al, 2005), no studies to date have investigated the role of ERa and ERb in these effects. Therefore, the goal of the present study was use ER selective agonists to identify the involvement of ERa and ERb in estrogen's ability to enhance reinstatement of cocaineseeking behavior in female OVX rats.…”

Prenatal Stress Enhances Responsiveness to Cocaine

“…followed by equithesin (0.5 ml/kg of a solution of 9.72 pentobarbital sodium, 42.5 chloral hydrate, and 21.3 mg/ml magnesium sulfate heptahydrate in 44% propylene glycol, 10% ethanol solution; i.p.) and chronic indwelling catheters were implanted in the right jugular vein as described previously (Kippin et al, 2005). Catheter patency was extended by daily administration of cefazolin (10.0 mg/ml; Schein Pharmaceutical, Florham Park, NJ) in heparinized saline (70 U/ml; Elkins-Sinn, Cherry Hill, NJ) and 0.1 ml of heparinized saline.…”

“…At the start of each session, the rat's catheter was connected to a motorized pump via a liquid swivel as described previously (Kippin et al, 2005) with the house light illuminated. Active lever presses resulted in a 2-s activation of the infusion pump and a 5-s presentation of a stimulus complex, consisting of activation of the white stimulus light above the active lever and the tone generator (78 dB, 2 kHz).…”