Presynaptic control of serotonin on striatal dopamine function
Psychopharmacology. 2010-10-16; 213(2-3): 213-242
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RATIONALE: 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.
CONCLUSION: 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.