ENTORHINAL CORTEX LESION OR INTRAHIPPOCAMPAL COLCHICINE INJECTION INCREASES PERIPHERAL TYPE BENZODIAZEPINE BINDING-SITES IN RAT HIPPOCAMPUS

The peripheral type benzodiazepine binding site (PTBBS) has been proposed to be a good marker for reactive glial cells following brain insults. In the present study, homogenate binding of H-3-Ro5-4864 and quantitative autoradiography of H-3-PK-11195 binding (two ligands for the PTBBS) were used to assess the distribution, time-course and extent of reactive gliosis in the hippocampus following deafferentation by unilateral entorhinal cortex lesion or neuronal death produced by intrahippocampal colchicine injection. Intrahippocampal colchicine injections produced a 3-fold increase in H-3-Ro5-4864 binding in the dentate gyrus within 2 days. This effect was doubled in animals pretreated with the lysosomal inhibitor chloroquine. Quantitative autoradiography of H-3-PK-11195 binding 1 or 2 weeks after colchicine injection indicated that the increase in binding was restricted to the dorsal hippocampus both rostrally and caudally and was present in the dentate gyrus and CA1. Following a unilateral electrolytic lesion of the entorhinal cortex, the binding of H-3-Ro5-4864 to homogenates of the dentate gyrus was doubled 18 h after the lesion, reached a maximum at 4 days post-lesion, and returned to control values by 2 months after the lesion. A transient increase in binding was also observed 2 and 4 days post-lesion in the dentate gyrus contralateral to the lesion side. Autoradiography of H-3-PK-11195 binding indicated that the increase in PTBBS following entorhinal cortex lesion was restricted to the molecular layer of the dendate gyrus. The results indicate that the extent, time-course and localization of the changes in PTBBS parallel the proliferation of microglial cells described following intrahippocampal colchicine injection and entorhinal cortex lesion, and support the use of the PTBBS as a marker for the quantitative evaluation of gliosis following a variety of brain insults.