Reversal of reserpine-induced vacuous chewing movements in rats by melatonin: involvement of peripheral benzodiazepine receptors

Several reports have indicated that melatonin modulates striatal dopaminerg ic functions via its interaction with central and peripheral benzodiazepine (BZ) receptors. Clinical reports and animal studies speculated on the poss ible involvement of melatonin in the pathophysiology of tardive dyskinesia (TD). In view of this, the present experiment was performed to study the po ssible effect of melatonin in modulation of reserpine-induced dyskinesia. M elatonin (1-10 mg/kg) dose dependently suppressed the severity of vacuous c hewing movements (VCMs) in rats. Prior administration of the putative melat onin receptor antagonists luzindole (2.5 and 5 mg/kg) or prazosin (2.5 and 5 mg/kg) failed to antagonize melatonin (2.5 mg/kg) reversal of reserpine-i nduced VCMs. However, the peripheral BZ receptor antagonist PK11195 (0.5 an d 1 mg/kg) but not flumazenil (1 and 2 mg/kg), dose dependently antagonized melatonin's reversal of reserpine-induced VCMs. Taken together the present results demonstrate that melatonin reverses reserpine-induced VCMs and tha t this could be due to enhancement of GABAergic activity via peripheral BZ receptors. (C) 2001 Elsevier Science B.V. All rights reserved.