THE INVOLVEMENT OF NORADRENALINE, 5-HYDROXYTRYPTAMINE AND ACETYLCHOLINE IN IMIPRAMINE-INDUCED SEIZURES IN MICE

The influence of some noradrenergic, 5-hydroxytryptaminergic and choli nergic agents on imipramine-induced seizures were investigated in mice . DL-threo-3,4-dihydroxyphenylserine (DOPS) and pargyline significantl y potentiated imipramine-induced seizures. Phentolamine and prazosin s ignificantly attenuated seizures elicited by imipramine and significan tly attenuated the seizure-enhancing effect of DOPS. Alpha-Methyl-p-ty rosine and reserpine significantly attenuated seizures induced by imip ramine. Disulfiram significantly protected mice against imipramine-ind uced seizures. However, DOPS significantly potentiated seizures induce d by imipramine in disulfiram-pretreated animals. Clonidine effectivel y protected mice against imipramine-induced seizures. Idazoxan, on the other hand, significantly protentiated seizures induced by imipramine and significantly antagonised the protective effect of clonidine agai nst the seizures. 5-HTP, PCPA, cyproheptadine, mianserin, ketanserin a nd trazodone did not affect imipramine-induced seizures to any signifi cant extent. Physostigmine antagonised seizures induced by imipramine while atropine significantly potentiated the seizures, and significant ly attenuated the protective effect of physostigmine against the seizu res. These data suggest that enhancement and attenuation of central no radrenergic and cholinergic neurotransmissions respectively, and not 5 -HT mechanisms, may underlie imipramine-induced seizures in mice.