Presynaptic control of serotonin on striatal dopamine function.
BACKGROUND
The influences of the serotonergic system on dopamine (DA) neuron activity have received considerable attention during the last three decades due to the real opportunity to improve disorders related to central DA neuron dysfunctions such as Parkinson's disease, schizophrenia, or drug abuse with serotonergic drugs. Numerous biochemical and behavioral data indicate that serotonin (5-HT) affects dopaminergic terminal function in the striatum.


OBJECTIVE
The authors propose a thorough examination of data showing controversial effects induced by striatal 5-HT on dopaminergic activity.


RESULTS
Inhibitory and excitatory effects of exogenous 5-HT have been reported on DA release and synthesis, involving various striatal 5-HT receptors. 5-HT also promotes an efflux of DA through reversal of the direction of DA transport. By analogy with the mechanism of action described for amphetamine, the consequences of 5-HT entering DA terminals might explain both the excitatory and inhibitory effects of 5-HT on presynaptic DA terminal activity, but the physiological relevance of this mechanism is far from clear. The recent data suggest that the endogenous 5-HT system affects striatal DA release in a state-dependent manner associated with the conditional involvement of various 5-HT receptors such as 5-HT(2A), 5-HT(2C), 5-HT(3), and 5-HT(4) receptors.


CONCLUSIONS
Methodological and pharmacological issues have prevented a comprehensive overview of the influence of 5-HT on striatal DA activity. The distribution of striatal 5-HT receptors and their restricted influence on DA neuron activity suggest that the endogenous 5-HT system exerts multiple and subtle influences on DA-mediated behaviors.
Unité Mixte de Recherche Centre National de la Recherche Scientifique 5227, Université Victor Segalen Bordeaux 2, Bordeaux, France.
Sylvia
S
Navailles
Philippe
P
De Deurwaerdère
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012559:Schizophrenia / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D004298:Dopamine