SEROTONERGIC MODULATION OF THE DISCRIMINATIVE-STIMULUS EFFECTS OF COCAINE IN SQUIRREL-MONKEYS

In order to investigate the potential modulatory role of serotonin on the discriminative-stimulus effects of cocaine, two groups of squirrel monkeys were trained to discriminate 0.3 mg/kg or 1.0 mg/kg cocaine a nd saline under a two-lever drug-discrimination procedure. Substitutio n of a range of cocaine doses (0.03-1.7 mg/kg) occasioned orderly, dos e-dependent increases in cocaine-lever responding. When administered a lone, the non-selective serotonin direct agonist, quipazine, also occa sioned increases in cocaine-lever responding which were more pronounce d in subjects trained with the lower cocaine dose. When quipazine was administered in combination with cocaine, there was an increase in coc aine-lever responding, indicating an additive effect. The serotonin up take inhibitor, fluoxetine, occasioned saline-lever responding when ad ministered alone. However, in combination with cocaine, fluoxetine enh anced the discriminative effects of cocaine in subjects trained at the lower cocaine dose. The 5-HT2-selective antagonists, ketanserin and r itanserin, did not occasion cocaine-lever responding when administered alone.