Effects of three monoamine uptake inhibitors on behavior maintained by cocaine or food presentation in rhesus monkeys.
Rhesus monkeys (n = 6) were surgically prepared with double lumen i.v. catheters and the effects of continuous infusion of the monoamine reuptake blockers mazindol, sertraline and fluoxetine were examined on behavior maintained by food presentation or i.v. cocaine injections. Under baseline conditions, lever pressing was maintained under a three-component multiple schedule of reinforcement in which food (1-g banana-flavored pellets) was available for 600 s under a fixed-ratio 30 schedule in the first and third components. In the second component, the dose of cocaine that maintained maximum rates of responding (0.03 or 0.05 mg/kg per injection) was available for 1800 s under a fixed-ratio 30 schedule. There was a brief time-out after each reinforcer. When behavior was stable, mazindol (0.4-3.2 mg/kg per 24 h), sertraline (0.1-8.0 mg/kg per 24 h) or fluoxetine (0.4-3.2 mg/kg per 24 h) was administered continuously via the second lumen of the double lumen catheter. Mazindol was administered for the same number of sessions that were required for responding to decline to low levels when the monkeys were allowed to self-administer saline [5-13] while sertraline and fluoxetine were administered for a minimum of 21 days. Baseline conditions were reinstated between doses of each drug. Each drug decreased cocaine-maintained responding in a dose-related manner. In most cases, food-maintained responding was disrupted at doses equal to or lower than those that decreased cocaine-maintained responding. Additionally, the higher doses of each drug decreased food intake outside the daily sessions. These results suggest that monoamine uptake blockers with prominent effects on either dopamine or serotonin neurotransmission can decrease cocaine self-administration but only at doses that also affect behavior maintained by other reinforcers.
Kleven
M S
MS
Department of Pharmacological and Physiological Sciences, University of Chicago, Pritzker School of Medicine, IL 60637.
Woolverton
W L
WL
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D008253:Macaca mulatta; D008454:Mazindol / Q000494:pharmacology*; D009042:Motivation; D012055:Reinforcement Schedule; D012646:Self Administration; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D020280:Sertraline
D015057:1-Naphthylamine; D003042:Cocaine; D005473:Fluoxetine; D008454:Mazindol; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline