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 dopaminerg ic projections from the substantia nigra, the striatum receives seroto nergic (5-HT) inputs arising from the raphe nuclei. To assess the puta tive role of striatal 5-HT in orofacial movements, serotonin (0, 0.2, 2, 10, 20 mu g/1.0 mu l) was infused into the ventrolateral striatum a nd behaviors were recorded using a time-sampling procedure. Serotonin produced a dose-dependent, site-specific increase in stereotyped orofa cial behaviors. Infusion of selective 5-HT receptor agonists or uptake inhibitors did not produce the orofacial syndrome and pretreatment wi th either selective or nonselective 5-HT receptor antagonists did not block the 5-HT induced stereotypy. In contrast, pretreatment with DA r eceptor antagonists completely abolished the 5-HT induced repetitive o rofacial movements, providing evidence for a 5-HT/DA interaction at th is 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 inte raction between 5-HT and DA in the striatum at presynaptic DA terminal s. It is hypothesized that 5-HT may cause release of DA via reversal o f the DA transporter. This syndrome may provide an animal model for so me aspects of obsessive-compulsive disorder, because current theories of this disorder implicate 5-HT dysfunction in the basal ganglia.