title: Synergism between buprenorphine and cocaine on the rotational behavior of the nigrally-lesioned rat.
abstract: Buprenorphine, a partial mu-opioid receptor agonist, has been proposed as a treatment for cocaine abuse. However, studies in animals have produced conflicting results on the nature of the interaction between buprenorphine and cocaine. In some studies, buprenorphine attenuated the effects of cocaine and in others it enhanced them. The purpose of the present study was to evaluate the interaction of buprenorphine and cocaine on the rotational behavior of the nigrally-lesioned rat. Both buprenorphine (0.003-0.1 mg/kg) and cocaine (1.0-30 mg/kg) alone produced dose-dependent increases in rotational behavior. Buprenorphine produced long-lasting turning with a peak at 60 min after administration, while cocaine produced turning that peaked immediately after administration and lasted for about 2 h. To distinguish simple additivity from other possible outcomes, we determined the relative potency of each drug alone, using a defined level of effect: 150 turns above the saline control in 4 h. This effect was produced by 10.0 mg/kg cocaine alone and by 0.0175 mg/kg buprenorphine alone. Based on these results, fixed ratio combinations were tested and the experimentally derived effects were compared to the theoretically additive values, using an isobolographic analysis. The fixed ratio combinations of the two drugs tested produced turning greater than predicted from simple additivity. This finding provides statistically-supported evidence for synergism between the actions of buprenorphine and cocaine.
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Kimmel
authors.forename: R J
authors.initials: RJ
authors.lastname: Tallarida
authors.forename: S G
authors.initials: SG
authors.lastname: Holtzman
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002047:Buprenorphine / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects*
chemical_list: D002395:Catecholamines; D004338:Drug Combinations; D009292:Narcotic Antagonists; D009294:Narcotics; D015102:3,4-Dihydroxyphenylacetic Acid; D002047:Buprenorphine; D003042:Cocaine