Serotonin synthesis inhibition in olivo-cerebellar system attenuates harmaline-induced tremor in Swiss albino mice.
Recent experimental evidences point to the active role of central serotonin (5-HT) elicited mechanisms in the pathogenesis of tremor. The present study was undertaken to investigate the effects of p-chlorophenylalanine (pCPA), a specific tryptophan hydroxylase inhibitor and a central 5-HT depletor, on the neurochemical processes that occur synchronously in olivary nucleus (ON) and cerebellum during harmaline-induced tremor in mice. Tremor appeared by 3-4 min following harmaline administration, and reached its peak by 25 min for the doses (10-30 mg/kg) studied. Peak of harmaline-tremor coincided with increases in 5-HT in ON and cerebellum, as assayed employing HPLC-electrochemistry. Administration of pCPA caused significant depletion in 5-HT level in both the regions analyzed, and also significantly inhibited harmaline-induced tremor. Our present results support the earlier electrophysiological evidences that harmaline-induced tremor originates from ON, and confirm the role of 5-HT in the genesis of this motor neuronal dysfunction.
Mehta
Hina
H
Division of Neurosciences, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Calcutta 700 032, India.
Saravanan
Karuppagounder S
KS
Mohanakumar
Kochupurackal P
KP
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D004347:Drug Interactions; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology*; D006246:Harmaline; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008996:Monoamine Oxidase Inhibitors; D009847:Olivary Nucleus / Q000187:drug effects* / Q000378:metabolism; D011149:Pons / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014202:Tremor / Q000139:chemically induced / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006246:Harmaline; D010134:Fenclonine; D004298:Dopamine