Title | Sex differences in selecting between food and cocaine reinforcement are mediated by estrogen. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Kerstetter KA, Ballis MA, Duffin-Lutgen S, Carr AE, Behrens AM, Kippin TE |
Journal | Neuropsychopharmacology |
Volume | 37 |
Issue | 12 |
Pagination | 2605-14 |
Date Published | 2012 Nov |
ISSN | 1740-634X |
Keywords | Analysis of Variance, Animals, Choice Behavior, Cocaine, Conditioning, Operant, Data Interpretation, Statistical, Estrogens, Estrous Cycle, Female, Food, Male, Ovariectomy, Rats, Rats, Sprague-Dawley, Reinforcement (Psychology), Sex Characteristics |
Abstract | 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. |
DOI | 10.1038/npp.2012.99 |
Alternate Journal | Neuropsychopharmacology |
PubMed ID | 22871910 |
PubMed Central ID | PMC3473343 |
Grant List | DA027115 / DA / NIDA NIH HHS / United States DA027525 / DA / NIDA NIH HHS / United States |