Effects of mazindol on behavior maintained or occasioned by cocaine.
The effects of mazindol, cocaine and D-amphetamine were studied in rhesus monkeys trained to self-administer cocaine, and in rats and squirrel monkeys trained to discriminate cocaine from saline. Non-contingent intravenous drug injections were administered to monkeys responding under a session consisting of a 5-min period during which lever-pressing produced food reinforcement and a 60-min session in which responding produced i.v. cocaine infusions (10 or 33 micrograms/kg per infusion). Acute i.v. injections of cocaine (0.1-1.7 mg/kg), D-amphetamine (0.1-1 mg/kg) and the dopamine re-uptake inhibitor mazindol (0.03-0.56 mg/kg) given 5 min before the session decreased self-administration of cocaine, but also decreased rates of behavior maintained by the presentation of food. In both rats and squirrel monkeys trained to discriminate cocaine from saline in a two-lever, food-maintained procedure, mazindol, cocaine and D-amphetamine substituted for cocaine in a dose-related manner. Despite a lack of selectivity to decrease cocaine self-administration as compared to behavior maintained by food, the present data provide some rationale for further consideration of mazindol as a potential pharmacotherapy for stimulant abuse, due to its relatively low abuse liability and cocaine-like discriminative stimulus effects.
Mansbach
R S
RS
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Balster
R L
RL
D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects; D001143:Arousal / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D003913:Dextroamphetamine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012453:Saimiri; D012646:Self Administration
D008454:Mazindol; D003042:Cocaine; D003913:Dextroamphetamine