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 neurolept ic 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 m odel of tardive dyskinesia, Chronic blockade of D-2 inhibitory dopamine (DA ) receptors localized on glutamatergic terminals in the striatum leads to t he persistent enhanced release of glutamate that kills the striatal output neurons. The object of the present study was to explore the role of glutama tergic modulation on the neuroleptic-induced VCMs, Rats were chronically (f or 21 days) treated with haloperidol (1.5 mg/ kg, i,p,) to produce VCMs. Th e 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 antago nist, dose dependently (0.02 and 0.05 mg/kg) reduced haloperidol-induced VC Ms. Felodipine (5 and 10 mg/kg), an L-type calcium-channel blocker, also si gnificantly 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 finding s of the present study indicated NMDA receptor involvement in haloperidol-i nduced VCMs, and also suggested the possible involvement of calcium and nit ric oxide in haloperidol-induced VCMs, (C) 2001 Lippincott Williams & Wilki ns.