M. Kamijima et Je. Casida, Regional modification of [H-3]ethynylbicycloorthobenzoate binding in mousebrain GABA(A) receptor by endosulfan, fipronil, and avermectin B-1a, TOX APPL PH, 163(2), 2000, pp. 188-194
[H-3]Ethynylbicycloorthobenzoate ([H-3]EBOB), a high affinity radioligand f
or the noncompetitive blocker site of the GABA, receptor, is used here for
quantitative autoradiography to determine regional binding in mouse brain a
nd 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 [H-3]EBOB
was determined for 20-mu m brain sections as the difference in labeling on
incubation with 2 nM [H-3]EBOB either alone (total binding) or with 5 mu M
alpha-endosulfan (nonspecific binding). The highest specific labeling was
observed for layers I and IV of the cerebral cortex, the globus pallidus, a
nd the medial septal nucleus/nucleus of the vertical limb of the diagonal b
and, Dose-dependent inhibition by endosulfan was highest in the nucleus acc
umbens and least in the cerebellum and periaqueductal gray matter. Fipronil
had much less effect on binding even at severely toxic doses. AVM increase
d [H-3]EBOB binding in most regions and was the only one of the three agent
s inhibiting in vitro [H-3]strychnine binding to the glycine receptor. In s
ummary, the noncompetitive blocker site was strongly inhibited with dose de
pendence and regional selectively by alpha-endosulfan but was generally poo
rly inhibited or activated by fipronil and was activated by avermectin, (C)
2000 Academic Press.