title: Serotonergic modulation of the activity of mesencephalic dopaminergic systems: Therapeutic implications.
abstract: Since their discovery in the mammalian brain, it has been apparent that serotonin (5-HT) and dopamine (DA) interactions play a key role in normal and abnormal behavior. Therefore, disclosure of this interaction could reveal important insights into the pathogenesis of various neuropsychiatric diseases including schizophrenia, depression and drug addiction or neurological conditions such as Parkinson's disease and Tourette's syndrome. Unfortunately, this interaction remains difficult to study for many reasons, including the rich and widespread innervations of 5-HT and DA in the brain, the plethora of 5-HT receptors and the release of co-transmitters by 5-HT and DA neurons. The purpose of this review is to present electrophysiological and biochemical data showing that endogenous 5-HT and pharmacological 5-HT ligands modify the mesencephalic DA systems' activity. 5-HT receptors may control DA neuron activity in a state-dependent and region-dependent manner. 5-HT controls the activity of DA neurons in a phasic and excitatory manner, except for the control exerted by 5-HT2Creceptors which appears to also be tonically and/or constitutively inhibitory. The functional interaction between the two monoamines will also be discussed in view of the mechanism of action of antidepressants, antipsychotics, anti-Parkinsonians and drugs of abuse.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5293, 33076 Bordeaux Cedex, France. Electronic address: deurwaer@u-bordeaux.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: De Deurwaerdère
authors.affiliation: Department of Physiology & Biochemistry, Faculty of Medicine and Surgery, University of Malta, Malta; Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, UK. Electronic address: giuseppe.digiovanni@um.edu.mt.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008636:Mesencephalon / Q000166:cytology* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D018490:Serotonin Agents; D012701:Serotonin; D004298:Dopamine
keywords: Antidepressant; Antipsychotic; Drug abuse; Electrophysiology; Microdialysis; Serotonin receptors