Sex and menstrual cycle effects on progressive ratio measures of cocaine self-administration in cynomolgus monkeys.
Fluctuations in ovarian steroid hormones across the menstrual/estrous cycle influence the abuse-related effects of acute cocaine administration in women and chronic cocaine self-administration in rodents, but there have been no comparable studies in non-human primates. The interactions among sex, menstrual cycle phase, and cocaine self-administration (0.0032, 0.01, and 0.032 mg/kg/injection (inj)) under a progressive ratio schedule were investigated in four female and two male cynomolgus monkeys. Females were given unrestricted access to cocaine across 54 menstrual cycles, and males were studied over 23 pseudo-cycles of 30 days duration. Ovulatory cycles were defined by luteal phase elevations in progesterone and 44 cycles were ovulatory. During ovulatory menstrual cycles, females reached significantly higher progressive ratio break points than males at all three unit doses of cocaine (P<0.001). During anovulatory cycles, females also reached significantly higher break points than males for 0.032 mg/kg/inj cocaine (P<0.01). Progressive ratio break points for cocaine (0.01 and 0.032 mg/kg/inj) did not vary significantly as a function of ovarian steroid hormone levels during the follicular and the luteal phase of ovulatory menstrual cycles, or during anovulatory cycles. Progressive ratio break points for 0.0032 mg/kg/inj cocaine were significantly higher during the follicular phase than during the late luteal phase (P<0.05-0.001). There were no systematic changes in progressive ratio break points in male pseudo-cycles. Significant cocaine dose-related sex differences were observed, but no consistent changes in cocaine self-administration as a function of menstrual cycle phase, or levels of estradiol and progesterone, were detected in female cynomolgus monkeys.
Mello
Nancy K
NK
Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. mello@mclean.harvard.edu
Knudson
Inge M
IM
Mendelson
Jack H
JH
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D008597:Menstrual Cycle / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000097:blood; D011863:Radioimmunoassay / Q000379:methods; D012055:Reinforcement Schedule; D012646:Self Administration / Q000379:methods; D012727:Sex Characteristics
D018765:Dopamine Uptake Inhibitors; D011374:Progesterone; D004958:Estradiol; D003042:Cocaine