Modification of behavioral effects of cocaine by selective serotonin and dopamine uptake inhibitors in squirrel monkeys.
Modification of the behavioral effects of cocaine by the selective serotonin (5-HT) uptake inhibitors citalopram and fluoxetine and the selective dopamine (DA) uptake inhibitor GBR 12909 was investigated in squirrel monkeys trained under a fixed-interval schedule of reinforcement or a two-lever cocaine-discrimination procedure. Under the fixed-interval schedule cocaine (0.03-1.78 mg/kg) produced dose-related increases in response rate, reaching an average maximum of 215% of control after a dose of 0.3 mg/kg. Similar rate-increasing effects were seen with GBR 12909 (3.0 or 10.0 mg/kg), but not citalopram (10.0 or 17.8 mg/kg) or fluoxetine (10.0 mg/kg). Pretreatment with citalopram or fluoxetine attenuated the rate-increasing effects of cocaine and produced an overall downward shift in the cocaine dose-response function. Pretreatment with GBR 12909, on the other hand, produced an overall leftward shift in the cocaine dose-response function. Under the drug-discrimination procedure cocaine (0.03-1.78 mg/kg) engendered dose-related increases in the percentage of cocaine-appropriate responses, as did GBR 12909 (1.0-17.8 mg/kg) but not citalopram (1.0-17.8 mg/kg). Pretreatment with citalopram attenuated the discriminative stimulus effects of cocaine and produced an overall rightward shift in the cocaine dose-response function, whereas pretreatment with GBR 12909 produced an overall leftward shift in the cocaine dose-response function. The results show that selective 5-HT and DA uptake inhibitors can modify the rate-altering and discriminative stimulus effects of cocaine in qualitatively different ways and suggest a modulatory role for 5-HT uptake inhibition in the behavioral effects of cocaine.
Spealman
R D
RD
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772-9102.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D012055:Reinforcement Schedule; D012453:Saimiri; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors