MODIFICATION OF 2,2',2''-TRIPYRIDINE-INDUCED TREMOR IN MICE BY SEROTONERGIC AGONISTS AND ANTAGONISTS AND BENZODIAZEPINES

The administration of 2,2 ',2 ''-tripyridine produced generalized trem or, myoclonus, and hindlimb abduction, similar to the ''5-hydroxytrypt amine (5-HT) syndrome,'' in mice. Pretreatment with mianserin, cyprohe ptadine, methysergide, or metergoline ameliorated, whereas 5-hydroxytr yptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), or 8-hy droxy-2-[di-n-propylamino]tetraline hydrobromide (8-OH-DPAT) augmented the 2,2 ',2 ''-tripyridine-induced tremor. Furthermore, diazepam and flunitrazepam exhibited a dose-dependent protection against 2,2 ',2 '' -tripyridine-induced tremor in mice, but pentobarbital only had a sli ghtly protective effect. The inhibitory effects of diazepam and flunit razepam on the 2,2 ',2 ''-tripyridine-induced tremor were potentiated in mice pretreated with-p-chlorophenylalanine (PCPA). These observatio ns suggest a serotonin-mediated action of 2,2 ',2 ''-tripyridine in it s tremor action and that the benzodiazepine agonist attenuation of the 2,2 ',2 ''-tripyridine-induced tremor is probably mediated through th e GABAergic inhibition of serotonergic neurons.