Electrical kindling of rats treated discontinuously or continuously with haloperidol.

Intermittent as opposed to continuous treatment of rats with haloperidol resulted in a long-lasting potentiation of oral activity. To examine if this behavioural sensitization to discontinuous neuroleptic treatment facilitates seizure development in electrical kindling, rats treated either intermittently or continuously with haloperidol for 15 weeks were kindled in the nucleus amygdala. Development of kindled seizures was significantly faster in the intermittently treated group (P < 0.01) than in controls or continuously treated rats. Furthermore, discontinuously treated animals displayed electroencephalographic afterdischarges in the substantia nigra from the beginning of treatment. The findings of cross-sensitivity between electrical amygdala kindling and pharmacological sensitization and of early appearance of epileptiform nigral activity have implications for the pathogenesis of both conditions. We suggest that depressed gamma-aminobutyric acid activity in substantia nigra could be a common mechanism.