title: Interactions among ovarian hormones and time of testing on behavioral sensitization and cocaine self-administration.
abstract: Ovarian hormones play a role in the use of drugs of abuse in women. In female rats estradiol has been shown to enhance acquisition of cocaine self-administration and behavioral sensitization induced by repeated cocaine treatment. Experiments were conducted to determine the effects of estradiol and/or progesterone on cocaine self-administration and behavioral sensitization to cocaine (10mg/kg; in animals with unilateral 6-hydroxydopamine lesions). Five groups of ovariectomized females were tested: (1) oil vehicle; (2) estradiol (E); (3) progesterone (P); (4) estradiol and progesterone given concurrently (EPC); (5) estradiol and progesterone given sequentially (EPS: 3 days of estradiol, 1 day progesterone, 1 day oil). All animals were tested during the dark phase of the light:dark cycle at ZT1600 and ZT2000-2100. Behavioral sensitization results: there was substantial conditioned turning throughout the habituation periods, and all animals exhibited behavioral sensitization with repeated cocaine treatment. Multivariate analysis indicated a significant effect of hormone treatment, time of day and day of testing. When individual groups were compared, however, only at ZT1600 did the E-treated and the EPS-treated animals show a trend (p<0.06) for greater behavioral sensitization to cocaine relative to the oil-treated animals. Self-administration results: all groups showed rapid acquisition of cocaine self-administration at 0.3 mg/kg/infusion, so we did not see an effect of ovarian hormones on acquisition, or a difference between groups tested at ZT1600 versus ZT2100 (p<0.05). There was, however, enhanced total intake of cocaine at 0.75 mg/kg/infusion in the E and the EPS groups. Concurrent administration of progesterone with estradiol counteracted the effect of estradiol on cocaine intake at 0.75 mg/kg/infusion, while progesterone alone did not enhance cocaine self-administration.
authors: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Hongyan
authors: H
authors: Yang
authors: Wei
authors: W
authors: Zhao
authors: Ming
authors: M
authors: Hu
authors: Jill B
authors: JB
authors: Becker
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000523:psychology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D015999:Multivariate Analysis; D010052:Ovariectomy / Q000379:methods; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration / Q000379:methods; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D012739:Gonadal Steroid Hormones; D011374:Progesterone; D004958:Estradiol; D003042:Cocaine
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