Factors responsible for increased excitability of dentate gyrus granule cells during exposure to lindane.

Rats were anesthetized with urethane, implanted with stimulating and recording electrodes in the perforant path and dentate gyrus, and exposed to different doses of lindane. Analysis of evoked field potential responses indicated that lindane exposure resulted in consistent, dose-dependent changes. Two separable effects were observed. First, lindane produced a small increase in the field excitatory postsynaptic potential (EPSP). Second, lindane produced much more significant effects upon granule cell excitability as evidenced by decreased threshold for evoking the field population spike (PS), increased amplitude of the PS and decreased latencies to PS onset and to peak. An analysis of these data suggests that presynaptic actions, e.g., increased transmitter release from perforant path terminals, do not appear to play an important role in the increased responsivity of granule cells. The most important factor appears to be a dose-dependent increase in the excitability of the granule cell due to other causes. In comparable studies, other subjects were prepared similarly and tested with other convulsive agents. Comparison of lindane to other convulsants revealed that lindane mimicked the changes produced in dentate gyrus responses by GABA antagonist drugs including picrotoxin, pentylenetetrazol and bicuculline. The glycine antagonist, strychnine, produced a different spectrum of effects. The data lend support to the hypothesis that an interaction of lindane with the GABA receptor-chloride channel complex is an important mechanism underlying both subconvulsant and convulsant actions. A reduction in tonic, GABA-mediated inhibition may be the basis for the increase in intrinsic granule cell excitability.