The role of different types of adrenergic receptors in pentylenetetrazol-induced seizures and the effect of di-n-propylacetate in the rat.

Abstract

Selective depletion of forebrain noradrenaline has been shown to potentiate various types of experimentally induced seizures. This study was aimed at exploring the role of different types of adrenergic receptors in pentylenetetrazol (PTZ)-induced seizures in rats and the anticonvulsive effect of di-n-propylacetate (DPA). Piperoxane (10 and 20 mg/kg, IP) significantly potentiated PTZ-induced tonic seizures and mortality. Similar effects were observed after 6-hydroxydopamine (6-OHDA)-induced depletion of forebrain noradrenaline, whereas no effects were found in animals with depletion of spinal noradrenaline. Neither phenoxybenzamine (20 mg/kg, IP) nor prazosin (1 and 10 mg/kg, IP) nor propranolol (2 and 5 mg/kg, IP) modified tonic seizures and mortality caused by PTZ. Combined treatment with propranolol (5 mg/kg, IP) and prazosin (10 mg/kg, IP) had no effect either. Various agents used to increase central serotonin transmission (d-fenfluramine, 5 mg/kg, IP; quipazine, 10 mg/kg, IP; m-chlorophenylpiperazine, 3 mg/kg, IP) did not alter the effect of piperoxane on PTZ-induced seizures. None of the conditions used to diminish central adrenergic function significantly affected the inhibitory effect of DPA on tonic seizures and mortality caused by PTZ. Combined treatment with subthreshold doses of clonidine (0.1 mg/kg, IP) and DPA (75 mg/kg, IP) significantly reduced tonic seizures and mortality caused by PTZ. The data suggest that alpha 2 type adrenoceptors are involved in the control of PTZ-induced seizures in rats. The peculiarity of the role of these receptors in the effect of PTZ is discussed.