Immunohistochemical and Western blotting techniques were employed to examine the alterations in immunostaining of the gamma-amino butyric acid (GABA) receptor subunits gamma 1/3 and 2 within the hippocampus of the rat brain at 1, 3, 7, 14, and 30 days after a unilateral perforant pathway lesion. At 1, 3, and 7 days post-lesion, we observed a remarkable decrease in gamma 1/3 neuropil staining in the deafferented zone (i.e., the outer molecular layer of the dentate gyrus ipsilateral to the lesion), although at 3 and 7 days post-lesion, staining intensity was considerably recovered. At 14 days post-lesion, the gamma 1/3 immunostaining was indistinguishable from that of controls and it appeared yet more robust at 30 days post-lesion. We also observed a slight decrease in gamma 2 neuropil staining until 7 days post-lesion, and an increase in gamma 2 staining at 30 days post-lesion. Western blot analysis demonstrated data that was relatively consistent with our immunohistochemical observations, although gamma 3 was hardly detectable. Our study suggests that gamma subunits of the GABA(A) receptor in the dentate gyrus display a plastic response to the deafferentation of the perforant pathway. (c) 2005 Elsevier Ireland Ltd. All rights reserved.