The role of the central serotonergic system in pilocarpine-induced seizures: receptor mechanisms.
Modification of central serotonergic transmission resulted in alterations of pilocarpine convulsive activity in male Wistar rats. Seizure activity was increased after pizotifen injection and the latency period to onset of convulsions was shortened in animals pretreated with mianserine and quipazine. Stimulation of 5-HT1A receptors with 8-hydroxy-di-N,N-propylaminotetralin (8-OH-DPAT) and blockade of 5-HT1B receptors with cyanopindolol resulted in seizure protection. Intracerebroventricular injections of 5,6-dihydroxytryptamine (5,6-DHT) did not change the protective effect of cyanopindolol. Other agents specifically affecting serotonergic receptors, the agonists 1-(3-chlorophenyl)piperazine (mCPP) and 5-methoxytryptamine (5-MT) and the antagonists spiperone, metergoline, methysergide, cyproheptadine and metoclopramide, did not influence pilocarpine-induced seizures. In conclusion, the present study suggests that the inhibition of pilocarpine-induced seizures may be mediated by stimulation of 5-HT1A and by blockade of 5-HT1B receptors, located probably on the cholinergic terminals.
Janusz
W
W
Department of Pharmacology, Medical School, Lublin, Poland.
Kleinrok
Z
Z
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010862:Pilocarpine; D010918:Pizotyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D010862:Pilocarpine; D010918:Pizotyline; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008784:Methysergide