Effects of chronic d-amphetamine administration on the reinforcing strength of cocaine in rhesus monkeys.
BACKGROUND
Agonist medications have been proven effective in treating opioid and nicotine dependence; results from clinical studies suggest that the indirect dopamine agonist d-amphetamine may reduce cocaine abuse. In preclinical studies, chronic d-amphetamine treatment decreased ongoing cocaine self-administration.


OBJECTIVE
The present study extended previous results by determining effects of chronic d-amphetamine treatment on the reinforcing strength of cocaine under conditions in which access to cocaine was suspended during d-amphetamine treatment.


METHODS
Daily operant conditioning sessions consisted of morning access to food pellets delivered under a 50-response fixed-ratio schedule and evening access to cocaine (0.005-0.48 mg/kg per injection, i.v.) under a progressive-ratio schedule. After responding maintained by 0.045 mg/kg per injection cocaine stabilized, self-administration sessions were suspended and d-amphetamine (0.01-0.1 mg/kg per hr, i.v.) was administered continuously for 5 days. On the following day, d-amphetamine treatment was discontinued and daily self-administration sessions resumed.


RESULTS
Following termination of d-amphetamine treatment, food- and cocaine-maintained responding was decreased in a dose-related manner. Decreases in the reinforcing strength of cocaine were larger and lasted longer than effects on food reinforcement. However, cocaine self-administration was unaltered if 6 days elapsed between discontinuation of d-amphetamine treatment and the next cocaine self-administration session.


CONCLUSIONS
The necessity of a self-administration session in the presence of d-amphetamine suggests that the protracted decrease in cocaine self-administration may be a manifestation of behavioral tolerance. Regarding treatment of cocaine dependence, data suggest that prolonged d-amphetamine treatment may be necessary to produce a sustained reduction in the reinforcing effects of cocaine.
Czoty
Paul W
PW
Department of Physiology and Pharmacology, Center for the Neurobiology of Addiction Treatments (CNAT), Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA.
Martelle
Jennifer L
JL
Nader
Michael A
MA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000008:administration & dosage*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D012054:Reinforcement, Psychology; D012646:Self Administration; D013997:Time Factors
D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D003042:Cocaine; D003913:Dextroamphetamine