Serotonergic stimulation of the ventrolateral striatum induces orofacial stereotypy

Dopaminergic (DA) stimulation of the ventrolateral striatum produces a syndrome of intense orofacial stereotypies. In addition to dopaminergic projections from the substantia nigra, the striatum receives serotonergic (5-HT) inputs arising from the raphe nuclei. To assess the putative role of striatal 5-HT in orofacial movements, serotonin (0, 0.2, 2, 10, 20 micrograms/1.0 microliters) was infused into the ventrolateral striatum and behaviors were recorded using a time-sampling procedure. Serotonin produced a dose-dependent, site-specific increase in stereotyped orofacial behaviors. Infusion of selective 5-HT receptor agonists or uptake inhibitors did not produce the orofacial syndrome and pretreatment with either selective or nonselective 5-HT receptor antagonists did not block the 5-HT induced stereotypy. In contrast, pretreatment with DA receptor antagonists completely abolished the 5-HT induced repetitive orofacial movements, providing evidence for a 5-HT/DA interaction at this site. Moreover, depletion of DA with a combination of reserpine and alpha-methyl-p-tyrosine markedly decreased the stereotyped behaviors induced by 5-HT microinfusion. These data provide evidence for an interaction between 5-HT and DA in the striatum at presynaptic DA terminals. It is hypothesized that 5-HT may cause release of DA via reversal of the DA transporter. This syndrome may provide an animal model for some aspects of obsessive-compulsive disorder, because current theories of this disorder implicate 5-HT dysfunction in the basal ganglia.