Serotonergic modulation of the activity of mesencephalic dopaminergic systems: Therapeutic implications
Progress in Neurobiology. 2017-04-01; 151: 175-236
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De Deurwaerdère P(1), Di Giovanni G(2).
(1)Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5293, 33076 Bordeaux Cedex, France.
(2)Department of Physiology & Biochemistry, Faculty of Medicine and Surgery, University of Malta, Malta; Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, UK.
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-HT2C receptors 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.
Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID: 27013075 [Indexed for MEDLINE]