Dissociation of stereotyped biting responses and oro-bucco-lingual dyskinesias

Abstract

A comparison was made of the doses of neuroleptic and related agents required to inhibit the stereotyped biting/gnawing/licking response induced in the guinea pig by systemically administered apomorphine and d-amphetamine or by dopamine administered bilaterally into the striatum. Haloperidol. lenperone, fluphenazine (0.5-8 mg/kg i.p.) and fluspirilene (0.125-8 mg/kg i.p.) each inhibited the stereotyped behaviour induced by apomorphine and amphetamine but doses up to 16 mg/kg i.p. failed to modify the dyskinesias induced by intrastriatal dopamine. Pimozide similarly abolished the stereotypies (0.125-8 mg/kg i.p.) but a larger dose (16 mg/kg i.p.) also abolished the dopamine-induced dyskinesias. However, oxiperomide and spiroxatrine were both shown to possess marked anti-dyskinetic (1-2 mg/kg i.p.) as well as anti-stereotypic (0.25-5 mg/kg i.p.) properties. Thioridazine, clothiapine, clozapine, sulpiride and metoclopramide were generally inactive against the stereotypies and dyskinesias although 1.25-5 mg/kg s.c. morphine effectively abolished stereotyped behaviour and the dopamine-induced dyskinesias were inhibited in a small proportion of animals. It is suggested that the dopamine mechanisms involved with stereotypy induction differ from those activated by intrastriatally administered dopamine to induce abnormal oro-facial movements, and that, since only the effects of intrastriatal dopamine showed the same relative degree of resistance to neuroleptic inhibition as clinical dyskinesias, that this may be more applicable to the clinical situation than the stereotypy model.