title: Reversal of reserpine-induced vacuous chewing movements in rats by melatonin: involvement of peripheral benzodiazepine receptors.
abstract: Several reports have indicated that melatonin modulates striatal dopaminergic functions via its interaction with central and peripheral benzodiazepine (BZ) receptors. Clinical reports and animal studies speculated on the possible involvement of melatonin in the pathophysiology of tardive dyskinesia (TD). In view of this, the present experiment was performed to study the possible effect of melatonin in modulation of reserpine-induced dyskinesia. Melatonin (1-10 mg/kg) dose dependently suppressed the severity of vacuous chewing movements (VCMs) in rats. Prior administration of the putative melatonin 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-induced VCMs. However, the peripheral BZ receptor antagonist PK11195 (0.5 and 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 that this could be due to enhancement of GABAergic activity via peripheral BZ receptors.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India.
authors.forename: V
authors.initials: V
authors.lastname: Raghavendra
authors.forename: P S
authors.initials: PS
authors.lastname: Naidu
authors.forename: S K
authors.initials: SK
authors.lastname: Kulkarni
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008409:Mastication / Q000187:drug effects* / Q000502:physiology; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D044094:Receptors, Melatonin; D012110:Reserpine / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D000970:Antineoplastic Agents; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011963:Receptors, GABA-A; D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D012110:Reserpine; D008550:Melatonin; D011224:Prazosin; C037850:PK 11195