title: The effects of heroin on prolactin levels in male rhesus monkeys: use of cumulative-dosing procedures.
abstract: There is considerable evidence that mu opioid receptors are involved in the regulation of anterior pituitary function. For example, in nonhuman primates and humans, mu agonists generally increase prolactin (PRL) levels. In contrast, mu antagonists decrease or have no effect on PRL levels. The goal of this study was to assess the potential utility of cumulative-dosing procedures to evaluate the endocrine effects of mu opioid receptor ligands. The effects of single and multiple, cumulative doses of the mu agonist heroin and the mu-selective antagonist quadazocine on PRL levels were investigated in four male rhesus monkeys. Cumulative dose-response curves were determined by infusing increasing drug doses at 60 min intervals over 290 min. Blood samples for PRL analysis were collected at 25 and 50 min after each cumulative infusion. Samples were collected at similar time points following single drug dose administration. Heroin (0.01-0.32 mg/kg, IV) administration dose-dependently increased PRL levels. Maximum levels of heroin-induced PRL levels were equivalent after single and cumulative doses. Quadazocine alone (0.032-1.0 mg/kg, IM) did not alter PRL levels significantly. However, quadazocine (0.1 mg/kg, IM) antagonized heroin-stimulated increases in PRL levels and produced a significant rightward shift in the heroin dose-effect curve. These data suggest that a cumulative-dosing procedure similar to that used in behavioral pharmacology may be useful to study the endocrine pharmacology of mu opioids in rhesus monkeys.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. cbowen@mclean.harvard.edu
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Bowen
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
authors.forename: Maureen
authors.initials: M
authors.lastname: Kelly
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Mello
mesh_terms: D000818:Animals; D001392:Azocines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D003932:Heroin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*
chemical_list: D001392:Azocines; D009292:Narcotic Antagonists; D009294:Narcotics; D017450:Receptors, Opioid, mu; D003932:Heroin; C035969:quadazocine