Effect of seizures kindled by subconvulsant doses of pentylenetetrazol on dopamine receptor binding and dopamine-sensitive adenylate cyclase in the rat

Abstract

Possible alterations in dopamine receptor regulation were assessed in pentylenetetrazol (PTZ)-kindled rats by examination of dopamine (DA)-sensitive adenylate cyclase activity and the specific binding of [ 3H]spiroperidol in various brain regions. A reduction in [ 3H]spiroperidol-labeled high-affinity binding sites in the amygdaloid-pyriform cortex followed the kindling of seizures by chronic administration of PTZ. Similarly, a reduction of low-affinity binding sites was observed in the frontal cortex of PTZ-kindled rats. No changes in the apparent affinity of both high- and low-affinity binding sites were found after kindling except in the amygdala-pyriform cortex. The affinity of the low-affinity binding site was significantly reduced in this brain region. The lack of significant changes in the number and affinity of binding sites after acute seizures induced by electroconvulsive shock or a convulsant dose of PTZ suggests that the changes in receptor binding after PTZ kindling were not related to seizure sequelae. Basal and DA-sensitive adenylate cyclase activities remained unchanged after PTZ kindling. In conjunction with our previous observations of significant alterations in [ 3H]spiroperidol binding after amygdaloid kindling, the present findings suggest that altered DA receptor regulation may be a general mechanism involved in the development of increased seizure susceptibility.