Triethyllead decreases central benzodiazepine receptor binding in rat cerebellum ex vivo

Effect of triethyllead on the specific [³H]flunitrazepam binding was studied in rat cortical and cerebellar P₂ fractions in vitro and in tissue homogenates of several rat brain regions ex vivo after 5 daily subcutaneous doses of 1.9 mg/kg triethyllead acetate to rats. Up to concentration of 100 μM, triethyllead did not significantly the specific [³H]flunitrazepam binding but attenuated marginally (14–18%) the GABA_A receptor agonist, muscimol-induced elevation of [³H]flunitrazepam binding in cerebellar tissue. After the subacute treatment of rats with triethyllead, the specific [³H]flunitrazepam binding was 27% lower in cerebellum compared to control animals. In other brain regions the receptor binding was not changed. The data suggest that triethyllead modified the cerebellar GABA_A receptor complex causing decreased binding in the benzodiazepine site. Such an inhibitory effect in the GABA_A receptor complex may decrease cerebellarinhibitory output and augment the triethyllead induced convulsions and tremor.