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.
Laboratory for Psychiatric Research, McLean Hospital, Belmont, MA 02178, USA.
S K
SK
Yeghiayan
A E
AE
Kelley
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005145:Face; D008297:Male; D008845:Microinjections; D009055:Mouth / Q000187:drug effects; D017072:Neostriatum / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013268:Stimulation, Chemical
D018759:Adrenergic Uptake Inhibitors; D018492:Dopamine Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D004298:Dopamine