Serotonin-dopamine interaction as a focus of novel antidepressant drugs.
Central serotonergic and dopaminergic systems play a critical role in the regulation of normal and abnormal behavior. Recent evidence suggests that a dysfunction of dopamine (DA) and serotonin (5-HT) neurotransmitter systems contributes to various pathological conditions. Among the multiple classes of 5-HT receptors described in the central nervous system, much attention has been devoted to the role of 5-HT2 receptor family in the control of central dopaminergic activity, because of the moderate to dense localization of both transcript and protein for 5-HT2A and 5-HT2C receptors in the substantia nigra (SN) and ventral tegmental area (VTA), as well as their terminal regions. Moreover, modulation of 5-HT2 receptor function by various drugs that has been shown to influence DA function in these brain areas is thought to be important in motor activation, motivation, and reward. Indeed, a number of electrophysiological and biochemical data have shown that 5-HT2C receptor agonists decrease, while 5-HT2C receptor antagonists enhance mesocorticolimbic DA function. Recent studies have focused on the functional interaction between the serotonergic and dopaminergic systems to explain the mechanism of the antidepressant action of SSRIs and 5-HT2 antagonists. In this article, the most relevant data regarding the role of these receptors in the control of brain DA function are reviewed, and the importance of this subject in the search of new antidepressant drugs is discussed.
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro (Chieti), Italy. esposito@negrisud.it
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D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D021381:Protein Transport; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
D000928:Antidepressive Agents; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D004298:Dopamine