Effects of serotoninergic drugs on tremor induced by physostigmine in rats

We investigated the effects of various serotoninergic drugs and serotonin ( 5-HT) depletion on physostigmine-induced visible tremor in rats. Physostigm ine (0.25-1.5 mg/kg) caused dose-dependent tremor, initiated at 3-5 min (la tency decreases as dose increases) and lasted for 30-35 min. Serotonin agon ists, 8-hydroxy-2-(di-n-propylamino) tetralin (2.5 mg/kg) and buspirone (5 mg/kg) augmented the tremor response caused by physostigmine. The 5-HT1/5-H T2 receptor antagonist, metergoline (1 mg/kg), and 5-HT2 blocker, cyprohept adine (10 mg/kg) significantly decreased the duration (40%) as well as inte nsity (45-50%) of physostigmine-tremor. The 5-HT2a/5-HT2c antagonist ritans erin (5 mg/kg) significantly reduced the duration (60%) without affecting t he intensity of the tremor. In 5-HT depleted rats (p-chlorophenylalanine; 3 00 mg/kg, for 3 days), physostigmine failed to produce tremor. Interestingl y, in these animals, administration of a non-specific 5-HT agonist, 5-metho xy-N,N-dimethyl tryptamine, caused high intensity tremor. These results sug gest that presence of 5-HT at the pre-synaptic terminals is needed for the tremor response by physostigmine and the response is greatly mediated via p ost-synaptic 5-HT receptors. The overall data indicated a direct involvemen t of central 5-HT system in the cholinergic tremor induced by physostigmine . (C) 2000 Elsevier Science B.V. All rights reserved.