REPEATED EXPOSURE TO LINDANE LEADS TO BEHAVIORAL SENSITIZATION AND FACILITATES ELECTRICAL KINDLING

Repeated intermittent exposure to some chemicals produces behavioral sensitization and seizure induction through a kindling mechanism. Although many pesticides are convulsant at high dosages, the persistent neurological effects of chronic low level exposure are unclear. The impact of intermittent exposure to lindane on behavioral seizure development and subsequent electrical kindling was assessed in the present study. Rats were administered lindane (0 or 10 mg/kg, po) for 30 days, or 3 times/week for 10 weeks. Enhanced behavioral responsiveness to lindane (myoclonic jerks, clonic seizures) emerged over the course of dosing and persisted 2 to 4 weeks after the last dose. The incidence of generalized convulsions was increased from 0% to 15% between the first and final day of dosing. In addition, electrographic recordings from the amygdala revealed brief rhythmic bursts and isolated interictal spike and wave discharge in the absence of overt behavioral seizures. Electrical kindling of the amygdala, beginning 4 to 6 weeks after the final dose, was facilitated. in contrast, prior administration of a single convulsive dose of lindane (20 mg/kg) was without effect on kindling development. These data indicate that repeated exposure to subconvulsant doses of lindane produces a persistent alteration in the central nervous system as evidenced by an enhanced susceptibility to kindled seizures. The pattern of behavioral development whereby the sensitivity is built up gradually over time is suggestive of a chemical kindling mechanism. Savings in the number of stimulation sessions required to induce electrical kindling following a history of lindane treatment provides further evidence that prior lindane exposure may lead to a state of partial kindling. Thus, intermittent subconvulsive lindane treatment induces alterations in limbic excitability that persist for at least 1 month.