title: The effects of amphetamine, butorphanol, and their combination on cocaine self-administration.
abstract: There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies. Once self-administration was acquired, rats were divided into four different groups and treated chronically for 20 days with (1) saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and butorphanol. During chronic treatment, cocaine self-administration was examined on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. On the FR schedule, butorphanol significantly decreased cocaine self-administration, but this effect was not enhanced by amphetamine. On the PR schedule, amphetamine and butorphanol non-significantly decreased cocaine self-administration when administered alone but significantly decreased cocaine self-administration when administered in combination. These data suggest that under some conditions (e.g., when the response requirement of cocaine is high), a dual stimulant-opioid pharmacotherapy may be more effective than a single-drug monotherapy.
authors.affiliation: Department of Psychology and Program in Neuroscience, Davidson College, Box 7037, Davidson, NC 28035-7037, United States. Electronic address: masmith@davidson.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.affiliation: Department of Psychology and Program in Neuroscience, Davidson College, Box 7037, Davidson, NC 28035-7037, United States.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Pennock
authors.affiliation: Department of Psychology and Program in Neuroscience, Davidson College, Box 7037, Davidson, NC 28035-7037, United States.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Pitts
authors.affiliation: Department of Psychology and Program in Neuroscience, Davidson College, Box 7037, Davidson, NC 28035-7037, United States.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Walker
authors.affiliation: Department of Psychology and Program in Neuroscience, Davidson College, Box 7037, Davidson, NC 28035-7037, United States.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Lang
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002077:Butorphanol / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004338:Drug Combinations; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D004338:Drug Combinations; D009294:Narcotics; D000661:Amphetamine; D003042:Cocaine; D002077:Butorphanol
keywords: Amphetamine; Butorphanol; Cocaine; Fixed ratio; Progressive ratio; Self-administration