Time-dependent pro- and anticonvulsant effects of cysteamine on the development and expression of amygdaloid kindled seizures

Abstract

The time-dependent pro- and anticonvulsant effects of cysteamine, a depletor of somatostatin, were investigated on the development and expression of amygdaloid kindled seizures. Acute administration of cysteamine (25–400 mg/kg, i.p.) produced a dose-dependent potentiation of kindled seizures when evoked 4 h after the drug. However, the seizures initiated 1 day after drug administration were dose-dependently suppressed. Furthermore, elicitation of seizures 4 h after cysteamine enhanced its anticonvulsant effects at 1 day after the drug, causing a parallel left shift of the dose-responsecurve. Since it has been reported that somatostatin is released during generalized seizures, the seizures given 4 h after cysteamine may encourage the somatostatin depletion by cysteamine and thereby potentiate its later anticonvulsant effects. The repeated administration of cysteamine (100 mg/kg, i.p.) during kindling development strongly retarded the development of generalized seizures but not the development of focal seizures or of afterdischarges in the amygdala. In contrast to the acute experiments, kindling stimulation given 4 h after each cysteamine treatment did not augment the blocking effect on kindling development. These data indicate that chronic cysteamine treatment has a strong inhibitory effect on the development of amygdaloid kindling.