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 tremor, myoclonus, and hindlimb abduction, similar to the "5-hydroxytryptamine (5-HT) syndrome," in mice. Pretreatment with mianserin, cyproheptadine, methysergide, or metergoline ameliorated, whereas 5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), or 8-hydroxy-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 slightly protective effect. The inhibitory effects of diazepam and flunitrazepam on the 2,2',2''-tripyridine-induced tremor were potentiated in mice pretreated with p-chlorophenylalanine (PCPA). These observations suggest a serotonin-mediated action of 2,2',2''-tripyridine in its tremor action and that the benzodiazepine agonist attenuation of the 2,2',2''-tripyridine-induced tremor is probably mediated through the GABAergic inhibition of serotonergic neurons.
Lin-Shiau
S Y
SY
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Hsu
K S
KS
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines; D002614:Chelating Agents / Q000008:administration & dosage / Q000633:toxicity*; D010134:Fenclonine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010424:Pentobarbital / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014202:Tremor / Q000139:chemically induced / Q000517:prevention & control*
D014151:Anti-Anxiety Agents; D002614:Chelating Agents; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D001569:Benzodiazepines; C013278:2,2',2''-terpyridine; D010424:Pentobarbital; D010134:Fenclonine