INFLUENCE OF SEROTONINERGIC DRUGS ON IN-VIVO DOPAMINE EXTRACELLULAR OUTPUT IN RAT STRIATUM

In vivo microdialysis was used to investigate the mechanism behind the increase in extracellular dopamine (DA) induced by increase in extrac ellular serotonin (5-HT) level and 5-HT1 and 5-HT2 receptor activation . The following serotoninergic drugs were perfused in the absence or p resence of nomifensine (5 mu M)or tetrodotoxin (TTX; 2 mu M): clomipra mine (PO, 500 and 1,000 mu M), a selective 5-HT reuptake inhibitor; 8- OH-DPAT (50 and 500 mu M), a 5-HT1A receptor agonist; and alpha-methyl -5-HT (1, 5 and 50 mu M), a 5-HT2 receptor agonist, All the serotonine rgic drugs studied increased DA extracellular output in a dose-depende nt manner. The presence of nomifensine attenuated the effect of perfus ion of clomipramine (500 mu M) and completely abolished the effect of perfusion of 8-OH-DPAT (500 mu M) and alpha-methyl-5-HT (5 mu M) on DA extracellular output. Clomipramine (100-1,000 mu M) perfusion produce d a dose dependent increase in DOPAC extracellular output, which was s tronger when clomipramine (500 mu M) was co-perfused with nomifensine. 8-OH-DPAT and alpha-methyl-5-HT perfusion decreased DOPAC overflow. A ddition of TTX to the perfusion fluid one hour before serotoninergic d rugs perfusion, did not completely abolish the effect on dopamine extr acellular output produced by the serotoninergic drugs. These data seem to indicate that increase in extracellular 5-HT level and 5-HT1 and 5 -HT2 receptor activation increase in vivo DA extracellular output in t he striatum mainly by a non-exocytotic mechanism involving DA uptake s ites and, secondarily, by activation of 5-HT receptors. (C) 1998 Wiley -Liss, Inc.