title: Effects of progesterone and testosterone on cocaine self-administration and cocaine discrimination by female rhesus monkeys.
abstract: 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.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA. mello@mclean.harvard.edu
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Mello
authors.forename: Inge M
authors.initials: IM
authors.lastname: Knudson
authors.forename: Maureen
authors.initials: M
authors.lastname: Kelly
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fivel
authors.forename: Jack H
authors.initials: JH
authors.lastname: Mendelson
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D003042:Cocaine / Q000008:administration & dosage*; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta; D011374:Progesterone / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D012646:Self Administration; D013739:Testosterone / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D013739:Testosterone; D011374:Progesterone; D003042:Cocaine