PHARMACOLOGICAL INTERACTIONS BETWEEN SEROTONIN AND DOPAMINE ON BEHAVIOR IN THE SQUIRREL-MONKEY

The behavioral effects of GBR 12909, a selective dopamine uptake inhib itor, were determined in squirrel monkeys trained to respond under a f ixed-interval (FI) schedule of stimulus termination and a second-order schedule of IV drug self-administration. Intermediate doses of GBR 12 909 increased FI response rate markedly, and the highest dose decrease d response rate below control values. The 5HT uptake inhibitors, alapr oclate and fluoxetine, and the 5HT agonist, quipazine, attenuated the behavioral-stimulant effects of CBR 12909, whereas the 5HT(2A/2C) anta gonist, ritanserin, enhanced the behavioral-stimulant effects of the l owest dose. GBR 12909 reliably maintained self-administration, and rit anserin increased response rate maintained by the highest dose. The do pamine agonist, quinpirole, increased Fl response rate in only one of three subjects, and ritanserin enhanced the behavioral-stimulant effec ts of quinpirole in that subject. The dopamine agonist, apomorphine, o nly decreased Fl response rate, and ritanserin did not alter its behav ioral effects, The pharmacological profile of GBR 12909 administered a lone and in combination with selective 5HT drugs in the present study was similar to that obtained previously with cocaine, further demonstr ating that 5HT can reliably modulate the behavioral effects of psychom otor stimulants with prominent dopaminergic actions.