TRIETHYLLEAD DECREASES CENTRAL BENZODIAZEPINE RECEPTOR-BINDING IN RATCEREBELLUM EX-VIVO

Effect of triethyllead on the specific [H-3]flunitrazepam binding was studied in rat cortical and cerebellar P-2 fractions in vitro and in t issue homogenates of several rat brain regions ex vivo after 5 daily s ubcutaneous doses of 1.9 mg/kg triethyllead acetate to rats. Up to con centration of 100 mu M, triethyllead did not affect significantly the specific [3H]flunitrazepam binding but attenuated marginally (14-18%) the GAB(A), receptor agonist, muscimol-induced elevation of [H-3]fluni trazepam binding in cerebellar tissue. After the subacute treatment of rats with triethyllead, the specific [H-3]flunitrazepam binding was 2 7% lower in cerebellum compared to control animals. In other brain reg ions the receptor binding was not changed. The data suggest that treit hyllead modified the cerebellar GAB(A), receptor complex causing decre ased binding in the benzodiazepine site. Such an inhibitory effect in the GAB(A), receptor complex may decrease cerebellar inhibitory output and augment the triethyllead induced convulsions and tremor.