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) elicite d by chronic neuroleptic administration in the rat, a possible model o f tardive dyskinesia (TD) in humans. The studies described here were u ndertaken in order to better determine whether this effect is mediated centrally or peripherally. In the first set of experiments, CCK-8S (1 0, 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., eve ry 3 weeks). A second set of experiments was then performed to determi ne if the previously observed effects of intraperitoneal CCK-8S were v agally mediated. As previously described, CCK-8S (10, 30 or 60 mug/kg, i.p.) suppressed neuroleptic-induced VCM's in sham-operated animals w ithout affecting the baseline VCM rate. Bilateral subdiaphragmatic vag otomy alone unexpectedly suppressed neuroleptic-induced VCM's to contr ol levels and CCK-8S had no further effect. Vagotomy also prevented th e suppressive effects of peripherally administered CCK-8S on rearing a nd grooming. We conclude that neuroleptic-induced VCM's may depend upo n 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.