PERSISTENT VACUOUS CHEWING IN RATS FOLLOWING NEUROLEPTIC TREATMENT - RELATIONSHIP TO DOPAMINERGIC AND CHOLINERGIC FUNCTION

In order to relate the effects of pharmacological intervention to neur oleptic induced increases in oral activity rats were treated continuou sly (7 mg/kg per week) or discontinuously (7 mg/kg per week or 2 mg/kg per week) with haloperidol for 6 months. Only the two intermittently treated groups developed persisting increases in vacuous chewing movem ents (VCM) following drug withdrawal. Opposed to control animals and c ontinuously treated rats, the discontinuously treated groups demonstra ted significant elevation in mouth movements following stimulation wit h the dopamine (DA) D-1 receptor agonist SK&F 38393 (23 mg/kg), wherea s they did not response to an acute challenge with the selective DA D- 1 receptor antagonist NNC-756 (0.1 mg/kg). The DA D-2 receptor antagon ist raclopride (1 mg/kg) provoked a general fall in VCM; however, this was only significant in rats treated intermittently with haloperidol 7 mg/kg per week and in control rats. Intermittent neuroleptic treatme nt also increased apomorphine-induced stereotypy. The effect of challe nge with the anticholinergic drug scopolamine (0.25 mg/kg) was not rel ated to oral activity; furthermore, the finding of severe agitation in rats tested with the latter drug points to caution in the interpretat ion of rating of rats treated with anticholinergics. These results sup port that intermittent ingestion of neuroleptic drugs lead to long-las ting increases in VCM. They also suggest a relation of persisting elev ated oral activity to supersensitivity to DA receptor agonists, as opp osed to subsensitivity to D-1 receptor antagonists.