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This unique pharmacological profile makes it a promising novel antipsychotic candidate. Preliminary clinical trials and animal experiments suggest that<jats:italic>l<\/jats:italic>\u2010SPD improves both positive and negative symptoms of schizophrenia without producing significant extrapyramidal side effects. To further explore the antipsychotic mechanisms of the drug, we studied the effects of<jats:italic>l<\/jats:italic>\u2010SPD on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) using in vivo single\u2010unit recording technique in rats.<jats:italic>Result:<\/jats:italic>We found that<jats:italic>l<\/jats:italic>\u2010SPD increased VTA DA neurons firing rate and induced slow oscillation in firing pattern. Moreover,<jats:italic>l<\/jats:italic>\u2010SPD, not clozapine, reversed d\u2010amphetamine\u2010induced inhibition which induced an excitation of VTA DA neurons. Furthermore, our data indicated that the excitatory effect of<jats:italic>l<\/jats:italic>\u2010SPD is associated with its partial agonistic action for the 5\u2010HT<jats:sub>1A<\/jats:sub>receptor since the 5\u2010HT<jats:sub>1A<\/jats:sub>receptor antagonist WAY100635 could block the<jats:italic>l<\/jats:italic>\u2010SPD\u2010induced excitatory effect. However, activation of 5\u2010HT<jats:sub>1A<\/jats:sub>receptor alone by specific agonist (\u00b1)\u20108\u2010Hydroxy\u20102\u2010(dipropylamino) tetralin (8\u2010OH\u2010DPAT) was insufficient to elicit excitation of VTA DA neurons, but the excitation of 8\u2010OH\u2010DPAT on VTA DA neurons was elicited in the presence of D<jats:sub>2<\/jats:sub>\u2010like receptors antagonist raclopride. Collectively, these results indicate that<jats:italic>l<\/jats:italic>\u2010SPD excited VTA DA neurons requiring its D<jats:sub>2<\/jats:sub>\u2010like receptors antagonistic activity and 5\u2010HT<jats:sub>1A<\/jats:sub>receptor agonistic activity.<jats:italic>Conclusion<\/jats:italic>: The present data demonstrate that D<jats:sub>2<\/jats:sub>receptor antagonist\/5\u2010HT<jats:sub>1A<\/jats:sub>receptor agonistic dual properties modulate dopaminergic transmission in a unique pattern that may underlie the different therapeutic responses between<jats:italic>l<\/jats:italic>\u2010SPD and other atypical antipsychotic drugs. Synapse, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/syn.20855","type":"journal-article","created":{"date-parts":[[2010,8,31]],"date-time":"2010-08-31T03:12:24Z","timestamp":1283224344000},"page":"379-387","source":"Crossref","is-referenced-by-count":19,"title":["<i>l<\/i>\u2010Stepholidine\u2010induced excitation of dopamine neurons in rat ventral tegmental area is associated with its 5\u2010HT<sub>1A<\/sub>receptor partial agonistic 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