Excitatory mechanisms in neuroleptic-induced vacuous chewing movements (VCMs): possible involvement of calcium and nitric oxide.
Tardive dyskinesia (TD) is a serious motor side-effect of chronic neuroleptic therapy. Chronic treatment with neuroleptics leads to the development of oral abnormal movements in rats known as vacuous chewing movements (VCMs). Vacuous chewing movements in rats have been widely accepted as an animal model of tardive dyskinesia. Chronic blockade of D2 inhibitory dopamine (DA) receptors localized on glutamatergic terminals in the striatum leads to the persistent enhanced release of glutamate that kills the striatal output neurons. The object of the present study was to explore the role of glutamatergic modulation on the neuroleptic-induced VCMs. Rats were chronically (for 21 days) treated with haloperidol (1.5 mg/kg, i.p.) to produce VCMs. The neuroleptic-induced VCMs viz., vertical jaw movements, tongue protrusions and bursts of jaw tremors, were counted during a 5 min observation period. Dizocilpine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, dose dependently (0.02 and 0.05 mg/kg) reduced haloperidol-induced VCMs. Felodipine (5 and 10 mg/kg), an L-type calcium-channel blocker, also significantly reduced the VCM count. N-omega-nitro-L-arginine methyl ester (L-NAME) (25 and 50 mg/kg), a nitric oxide synthase inhibitor, also reduced the VCM count in an L-arginine-sensitive manner. In conclusion, the findings of the present study indicated NMDA receptor involvement in haloperidol-induced VCMs, and also suggested the possible involvement of calcium and nitric oxide in haloperidol-induced VCMs.
Naidu
P S
PS
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D002118:Calcium / Q000502:physiology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D018698:Glutamic Acid / Q000502:physiology; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D008409:Mastication / Q000187:drug effects*; D016202:N-Methylaspartate / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects*
D014150:Antipsychotic Agents; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D006220:Haloperidol; D002118:Calcium