Effects of cannabinoid CB1 receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys

Abstract

Antipsychotic drugs may cause extrapyramidal symptoms (EPS), such as dyskinesia and dystonia. These effects are believed to involve dysfunctional striatal dopamine transmission. Patients with schizophrenia show increased prevalence of cannabis abuse and this has been linked to severity of EPS. Endocannabinoids modulate striatal dopamine activity via type 1 cannabinoid (CB1) receptors, and studies in rats and humans suggest beneficial effects of CB1 ligands on EPS. The present study explored the effects of CB1 receptor ligands on oral dyskinesia induced by the dopamine D1 receptor agonist SKF81297 (SKF) and acute dystonia induced by the dopamine D2 receptor antagonist haloperidol in Cebus apella monkeys. The monkeys were sensitised to EPS by prior exposure to D2 receptor antagonists.SKF (0.3 mg/kg) was administered alone and in combination with the CB1 agonist CP55,940 (0.0025–0.01 mg/kg) or the CB1 antagonist SR141716A (0.25–0.75 mg/kg). Haloperidol (individual doses at 0.01–0.02 mg/kg) was administered alone and in combination with CP55,940 (0.005 or 0.01 mg/kg) or SR141716A (0.5 or 0.75 mg/kg). Subsequently, the monkeys were videotaped, and the recordings were rated for oral dyskinesia or dystonia.SKF-induced oral dyskinesia was dose-dependently reduced by CP55,940, with no effect of SR141716A. Haloperidol-induced dystonia was not affected by either CP55,940 or SR141716A.