MONOAMINE INTERACTIONS MEASURED BY MICRODIALYSIS IN THE VENTRAL TEGMENTAL AREA OF RATS TREATED SYSTEMICALLY WITH (+ -)-8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN/

The effect of (+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT ), a selective serotonin 5-HT1A agonist, on levels of extracellular no repinephrine (NE), dopamine (DA), and 5-HT (measured simultaneously) w as investigated by microdialysis in the ventral tegmental area (VTA) o f freely moving rats, and their behavioral activity was monitored. At 50 mu g/kg s.c., 8-OH-DPAT reduced 5-HT levels but enhanced NE and DA levels in VTA dialysate. These effects were not altered by pretreatmen t with systemic idazoxan (5 mg/kg i.p.), a selective alpha(2) antagoni st, or local sulpiride (10 mu M), a Selective D-2/D-3 antagonist. At 5 00 mu g/kg s.c., 8-OH-DPAT further enhanced or more persistently reduc ed dialysate NE or 5-HT content but had little effect on dialysate DA content. Its DA level-increasing effect could be seen dramatically wit h local infusion of cocaine (30 mu M) and, to a lesser extent, sulpiri de (10 mu M). Depletion of endogenous 5-HT with p-chlorophenylalanine attenuated both the 5-HT level-reducing and DA level-enhancing effects of 8-OH-DPAT without affecting its maximal NE effect and the locomoto r-stimulatory effect. Partial depletion of endogenous NE with N-(2-chl oroethyl)-N-ethyl-2-bromobenzylamine failed to change the monoamine re sponse but diminished the locomotion induced by 8-OH-DPAT. These resul ts suggested that (a) the low dose of 8-OH-DPAT may act at presynaptic 5-HT1A receptors to modulate 5-HT and DA release, while acting at pos tsynaptic 5-HT1A receptors to modulate NE release; (b) the high dose o f 8-OH-DPAT may activate D-2 receptors to offset its DA level-increasi ng effect; and (c) the locomotor-stimulatory effect of 8-OH-DPAT might be mediated primarily by postsynaptic 5-HT1A receptors and the NE sys tem.