Effects of estradiol on cocaine self-administration and cocaine discrimination by female rhesus monkeys.
The ovarian steroid hormone, estradiol, enhances the reinforcing and locomotor activating effects of cocaine in rodents under some conditions. The present study evaluated the acute effects of estradiol benzoate (E(2)beta) on cocaine self-administration and cocaine discrimination in female rhesus monkeys. Cocaine self-administration (0.10 mg/kg/inj., i.v.) was maintained on a fixed-ratio (FR) 30 schedule of reinforcement, and monkeys had access to cocaine during one 2-h session each day. E(2)beta in a cyclodextrin vehicle (0.00001-0.01 mg/kg, i.m.) was administered 30 min before test sessions conducted twice each week. Cocaine doses were administered in an irregular order during each dose-effect curve determination (0.001-0.3 mg/kg/inj.). Blood samples were collected after test sessions to determine 17beta-estradiol levels. Banana-flavored food pellets were available on an FR 30 schedule in three 1-h sessions each day. Five monkeys were trained to discriminate cocaine (0.18 mg/kg, i.m.) from saline in a two-key food-reinforced procedure, and the effects of pretreatment with E(2)beta in cyclodextrin and in sesame oil were studied. Acute administration of E(2)beta did not consistently alter the cocaine self-administration or drug discrimination dose-effect curves in comparison to saline control treatment. Females also did not self-administer E(2)beta (0.00001-0.10 mg/kg, i.v.) above saline levels. Finally, E(2)beta (0.0001-0.01 mg/kg, i.m.) did not substitute for cocaine in monkeys trained to discriminate cocaine from saline. Taken together, these data suggest that over the dose range studied, estradiol administration does not consistently alter the abuse-related effects of cocaine in female rhesus monkeys.
Mello
Nancy K
NK
Department of Psychiatry, Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, Belmont, MA 02478, USA. mello@mclean.harvard.edu
Negus
S Stevens
SS
Knudson
Inge M
IM
Kelly
Maureen
M
Mendelson
Jack H
JH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D003270:Contraceptive Agents / Q000097:blood / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D005260:Female; D008253:Macaca mulatta; D011863:Radioimmunoassay; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000379:methods; D013997:Time Factors
D003270:Contraceptive Agents; D018765:Dopamine Uptake Inhibitors; C074283:estradiol 3-benzoate; D004958:Estradiol; D003042:Cocaine