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 harm aline-induced tremor originates from ON, and confirm the role of 5-HT in the genesis of this motor neuronal dysfunction. (C) 2003 Elsevier Science B.V. All rights reserved.