Regional modification of [(3)H]Ethynylbicycloorthobenzoate binding in mouse brain GABA(A) receptor by endosulfan, fipronil, and avermectin B(1a).

[(3)H]Ethynylbicycloorthobenzoate ([(3)H]EBOB), a high affinity radioligand for the noncompetitive blocker site of the GABA(A) receptor, is used here for quantitative autoradiography to determine regional binding in mouse brain and the effects on this binding of administering toxic doses of endosulfan, fipronil, and avermectin B(1a) (AVM). Animals were euthanized 4-8 min after 1 LD50 or 2 LD50 doses of the two channel blockers and 32 min after 1 LD50 or 4 LD50 doses of the channel activator AVM. Specific binding of [(3)H]EBOB was determined for 20-microm brain sections as the difference in labeling on incubation with 2 nM [(3)H]EBOB either alone (total binding) or with 5 microM alpha-endosulfan (nonspecific binding). The highest specific labeling was observed for layers I and IV of the cerebral cortex, the globus pallidus, and the medial septal nucleus/nucleus of the vertical limb of the diagonal band. Dose-dependent inhibition by endosulfan was highest in the nucleus accumbens and least in the cerebellum and periaqueductal gray matter. Fipronil had much less effect on binding even at severely toxic doses. AVM increased [(3)H]EBOB binding in most regions and was the only one of the three agents inhibiting in vitro [(3)H]strychnine binding to the glycine receptor. In summary, the noncompetitive blocker site was strongly inhibited with dose dependence and regional selectively by alpha-endosulfan but was generally poorly inhibited or activated by fipronil and was activated by avermectin. Copyright 2000 Academic Press.