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

Anker, Justin J.; Holtz, Nathan A.; Zlebnik, Natalie E.; Carroll, Marilyn E.

doi:10.1007/s00213-008-1371-9

Cited by 73 publications

(80 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, similar to female rats, drug-experienced women appear to devalue food (and perhaps other natural reinforcers) relative to taking drugs to a greater extent than men, which is likely a significant contributor to the more severe profile of cocaine dependence that women display. Future projects are required to assess the role of estrogen in cocaine choice in a more detailed fashion, as well as examine the effect of other ovarian hormones (eg, progesterone and its metabolite, allopregnanolone) on cocaine choice, as this ovarian hormone has been shown to decrease motivation for cocaine in single reinforcer studies (Feltenstein et al, 2009;Anker et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Selecting Between Food and Cocaine Reinforcement are Mediated by Estrogen

Kerstetter

Ballis

Duffin-Lutgen

et al. 2012

Neuropsychopharmacol

105

View full text Add to dashboard Cite

Cocaine-dependent women, relative to their male counterparts, report shorter cocaine-free periods and report transiting faster from first use to entering treatment for addiction. Similarly, preclinical studies indicate that female rats, particularly those in the estrus phase of their reproductive cycle, show increased operant responding for cocaine under a wide variety of schedules. Making maladaptive choices is a component of drug dependence, and concurrent reinforcement schedules that examine cocaine choice offers an animal model of the conditions of human drug use; therefore, the examination of sex differences in decision-making may be critical to understanding why women display a more severe profile of cocaine addiction than men. Accordingly, we assessed sex and estrous cycle differences in choice between food (45 mg grain pellets) and intravenous cocaine (0.4 or 1.0 mg/kg per infusion) reinforcement in male, female (freely cycling), and ovariectomized (OVX) females treated with either estrogen benzoate (EB; 5 μg per day) or vehicle. At both cocaine doses, intact female rats choose cocaine over food significantly more than male rats. However, the estrous cycle did not impact the level of cocaine choice in intact females. Nevertheless, OVX females treated with vehicle exhibited a substantially lower cocaine choice compared with those receiving daily EB or to intact females. These results demonstrate that intact females have a greater preference for cocaine over food compared with males. Furthermore, this higher preference is estrogen-dependent, but does not vary across the female reproductive cycle, suggesting that ovarian hormones regulate cocaine choice. The present findings indicate that there is a biological predisposition for females to forgo food reinforcement to obtain cocaine reinforcement, which may substantially contribute to women experiencing a more severe profile of cocaine addiction than men.

show abstract

Section: Discussionmentioning

confidence: 99%

Sex Differences in Selecting Between Food and Cocaine Reinforcement are Mediated by Estrogen

Kerstetter

Ballis

Duffin-Lutgen

et al. 2012

Neuropsychopharmacol

105

View full text Add to dashboard Cite

show abstract

“…With limited access to intravenous cocaine self-administration, female rats show more nonreinforced responding and a prolongation of extinction Fuchs et al, 2005;Kosten and Zhang, 2008). Under similar conditions, female rats also responded more to cocaine-induced reinstatement (Lynch and Carroll, 2000;Anker et al, 2009). In studies that used prolonged access to cocaine (24-hour access in discrete trials), female rats also showed enhanced responding on a progressive-ratio schedule during reinstatement after abstinence without extinction compared with males (Lynch and Taylor, 2004).…”

Section: Sex Differences In the Preoccupationmentioning

confidence: 99%

“…Progesterone and allopregnanolone (the levels of which are low during the estrous phase in rats) both selectively blocked cocaine-primed reinstatement only in female rats, and the effects of progesterone were blocked by finasteride, a drug that blocks the conversion of progesterone to allopregnanolone (Anker et al, 2009), suggesting a role for progesterone in drug-primed cocaine reinstatement. Estradiol, in contrast, increased cocaine-primed reinstatement in limited-access conditions .…”

Section: Effects Of Hormones During the Reproductive Cycle In Femamentioning

confidence: 99%

Sex Differences in Animal Models: Focus on Addiction

2016

View full text Add to dashboard Cite

“…In ovariectomized rats, progesterone inhibited estradiol enhancement of acquisition of cocaine self-administration (Jackson et al, 2006). Both progesterone and its major metabolite, allopregnanolone, blocked reinstatement of cocaine self-administration (Anker et al, , 2009, as well as escalation of cocainemaintained responding ; see for a review, Anker and Carroll, 2010).…”

Section: Introductionmentioning

confidence: 99%

Effects of Progesterone and Testosterone on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys

Mello

Knudson

Kelly

et al. 2011

Neuropsychopharmacol

View full text Add to dashboard Cite

The neuroactive steroid hormone progesterone attenuates cocaine's abuse-related effects in women and in rodents under some conditions, but the effects of testosterone are unknown. We compared the acute effects of progesterone (0.1, 0.2, and 0.3 mg/kg, intramuscularly (i.m.)), testosterone (0.001, 0.003, and 0.01 mg/kg, i.m.), and placebo on cocaine self-administration and cocaine discrimination dose-effect curves in female rhesus monkeys. Cocaine self-administration (0.03 mg/kg per inj.) was maintained on a fixed ratio 30 schedule of reinforcement, and monkeys had unlimited access to cocaine for 2 h each day. Cocaine doses were administered in an irregular order during each dose-effect curve determination, and the same dose order was used in each subject in all treatment conditions. Blood samples for hormone analysis were collected at the end of each test session. Banana-flavored food pellets (1 g) were also available in three 1-h daily sessions. In drug discrimination studies, the effects of pretreatment with progesterone (0.032-0.32 mg/kg, i.m.) and testosterone (0.001-0.01 mg/kg, i.m.) on the discriminative stimulus effects of cocaine (0.18 mg/kg, i.m.) were examined. Progesterone and testosterone did not alter cocaine discrimination, and did not substitute for cocaine. In contrast, progesterone and testosterone each significantly decreased cocaine self-administration, and produced a downward and rightward shift in the cocaine self-administration dose-effect curve. These findings are concordant with clinical reports that progesterone administration may decrease ratings of positive subjective effects of cocaine in women, and suggest the possible value of neuroactive steroid hormones for the treatment of cocaine abuse and reduction of risk for relapse.

show abstract

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

Abstract: These findings suggest that ALLO may explain part of PROG's inhibitory effect on cocaine-primed reinstatement, and it may serve as a novel approach for preventing relapse in female cocaine abusers.

Cited by 73 publications

References 69 publications

Sex Differences in Selecting Between Food and Cocaine Reinforcement are Mediated by Estrogen

Sex Differences in Selecting Between Food and Cocaine Reinforcement are Mediated by Estrogen

Sex Differences in Animal Models: Focus on Addiction

Effects of Progesterone and Testosterone on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys

Contact Info

Product

Resources

About