title: Effects of the mixed-action kappa/mu opioid agonist 8-carboxamidocyclazocine on cocaine- and food-maintained responding in rhesus monkeys.
abstract: The present study evaluated the effects of 8-carboxamidocyclazocine (8-CAC), a novel mixed-action kappa/mu agonist with a long duration of action, on food- and cocaine-maintained responding in rhesus monkeys to assess the potential utility of 8-CAC as a medication for the treatment of cocaine dependence. The effects of acute and chronic (10 days) 8-CAC were examined in rhesus monkeys responding under a multiple schedule for both cocaine and food reinforcement. Acute 8-CAC (0.032-0.56 mg/kg, i.m.) dose-dependently eliminated cocaine-maintained responding in all three monkeys. However, doses of 8-CAC that decreased cocaine self-administration typically also decreased food-maintained responding, and 8-CAC-induced decreases in cocaine self-administration diminished during chronic 8-CAC treatment. These results confirm that 8-CAC acutely decreases cocaine self-administration. However, non-selective effects of 8-CAC on food-maintained responding and tolerance to 8-CAC effects on cocaine self-administration may limit its potential for the treatment of cocaine dependence.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
authors.forename: Glenn W
authors.initials: GW
authors.lastname: Stevenson
authors.forename: Mark P
authors.initials: MP
authors.lastname: Wentland
authors.forename: Jean M
authors.initials: JM
authors.lastname: Bidlack
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Mello
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005502:Food; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012055:Reinforcement Schedule; D012201:Reward; D014839:Vomiting / Q000139:chemically induced
chemical_list: C459385:8-carboxamidocyclazocine; D006993:Hypnotics and Sedatives; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D003042:Cocaine; D003496:Cyclazocine