Effect of 5-HT1A and 5-HT2A/2C receptor modulation on neuroleptic-induced vacuous chewing movements

Tardive dyskinesia is a serious motor side effect of chronic neuroleptic th erapy. Chronic treatment or rats with neuroleptics leads to the development of abnormal oral movements called vacuous chewing movements. Vacuous chewi ng movements in rats are widely accepted as an animal model of tardive dysk inesia. Atypical antipsychotics such as clozapine and rispiridone are assoc iated with a lower incidence of extrapyramidal side effects and tardive dys kinesia. The present study was aimed to explore the role of 5-HT1A, 5-HT2A/ 2C receptors in the expression of neuroleptic-induced orofacial dyskinesia. In the present study rats were chronically (for 21 days) treated with halo peridol (1.5 mg/kg, i.p.) to elicit vacuous chewing movements. The neurolep tic-induced vacuous chewing movements, viz., vertical jaw movements. tongue protrusions and bursts of jaw tremors, were counted during a 5-min observa tion period. Acute treatment with 8-hydroxy-2-(di-n-propylamino) tetralin ( 8-OH-DPAT), a 5-HT1A receptor agonist, dose-dependently (0.05, 0.1 and 0.2 mg/kg, i.p.) reduced the haloperidol- induced vacuous chewing movements and headshakes. Both acute and chronic administration of seganserin, ketanseri n and ritanserin, 5-HT2A/2C receptor antagonists. also reduced haloperidol- induced vacuous chewing movements in a dose-dependent (0.05, 0.1 and 0.2 mg /kg, i.p.) manner. In acute studies a higher dose of ritanserin 1 mg/kg) bu t not ketanserin 1 mg/kg) increased vacuous chewing movements, whereas a hi gher dose of seganserin (1 mg/kg) did not have any effect on vacuous chewin g movements. All the drugs reduced haloperidol-induced headshakes in a dose -dependent fashion. These findings indicate that the serotonergic system, a nd particularly 5-HT1A and 5-HT-(2A/2C) receptors, may be involved in halop eridol- induced orofacial dyskinesia, and that 5-HT receptors may provide n ovel targets for the development of drugs that can be used to reverse or pr event the extrapyramidal side effects associated with long-term antipsychot ic treatment. (C) 2001 Elsevier Science B.V. All rights reserved.