Neuroleptic-induced chewing movements in the rat are suppressed by peripherally but not centrally administered CCK and abolished by bilateral subdiaphragmatic vagotomy.
We have previously demonstrated that intraperitoneal cholecystokinin (CCK-8S) suppresses the vacuous chewing mouth movements (VCM's) elicited by chronic neuroleptic administration in the rat, a possible model of tardive dyskinesia (TD) in humans. The studies described here were undertaken in order to better determine whether this effect is mediated centrally or peripherally. In the first set of experiments, CCK-8S (10, 30 or 50 ng, i.c.v.) was found to have no effect on VCM's elicited by 20 weeks treatment with fluphenazine decanoate (25 mg/kg, i.m., every 3 weeks). A second set of experiments was then performed to determine if the previously observed effects of intraperitoneal CCK-8S were vagally mediated. As previously described, CCK-8S (10, 30 or 60 micrograms/kg, i.p.) suppressed neuroleptic-induced VCM's in sham-operated animals without affecting the baseline VCM rate. Bilateral subdiaphragmatic vagotomy alone unexpectedly suppressed neuroleptic-induced VCM's to control levels and CCK-8S had no further effect. Vagotomy also prevented the suppressive effects of peripherally administered CCK-8S on rearing and grooming. We conclude that neuroleptic-induced VCM's may depend upon tonic activity in the vagus nerve and/or its central projections and that the effects of CCK-8S on this behavioural response are likely to be peripherally mediated.
Stoessl
A J
AJ
Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada.
Polanski
E
E
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008409:Mastication / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D014150:Antipsychotic Agents; D012844:Sincalide