title: 17β-estradiol is necessary for extinction of cocaine seeking in female rats.
abstract: Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17β-estradiol (E₂) affects expression and extinction of cocaine seeking in female rats. Using a conditioned place preference (CPP) paradigm, ovariectomized rats were maintained throughout conditioning with 2 d of E₂ treatment followed by 2 d of vehicle treatment, or were injected with E₂ daily. Hormone injections were paired or explicitly unpaired with place conditioning sessions. Expression of a cocaine CPP was of equal magnitude regardless of conditioning protocol, suggesting that E₂ levels during conditioning did not affect subsequent CPP expression. During extinction, daily E₂ administration initially enhanced expression of the cocaine CPP, but resulted in significantly faster extinction compared to controls. Whereas E₂-treated rats were extinguished within 8 d, vehicle-treated rats maintained CPP expression for more than a month, indicative of perseveration. To determine whether E₂ could rescue extinction in these rats, half were given daily E₂ treatment and half were given vehicle. E₂-treated rats showed rapid extinction, whereas vehicle-treated rats continued to perseverate. These data demonstrate for the first time that E₂ is necessary for extinction of cocaine seeking in female rats, and that it promotes rapid extinction when administered daily. Clinically, these findings suggest that monitoring and maintaining optimal E₂ levels during exposure therapy would facilitate therapeutic interventions for female cocaine addicts.
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Twining
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Tuscher
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Doncheck
authors.forename: Karyn M
authors.initials: KM
authors.lastname: Frick
authors.forename: Devin
authors.initials: D
authors.lastname: Mueller
mesh_terms: D000818:Animals; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003213:Conditioning, Psychological; D058999:Drug-Seeking Behavior / Q000502:physiology*; D004958:Estradiol / Q000378:metabolism*; D005108:Extinction, Psychological / Q000502:physiology*; D005260:Female; D010052:Ovariectomy; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D004958:Estradiol