SPATIOTEMPORAL CHANGES IN HIPPOCAMPAL NMDA RECEPTOR-BINDING AS A CONSEQUENCE OF TRIMETHYLTIN NEUROTOXICITY IN THE RAT

In the present study we examined the presumable changes in the distrib ution of N-methyl-D-aspartate (NMDA) receptors in the hippocampus of r at exposed to a potent neurotoxic drug, trimethyltin (TMT). Using in v itro receptor binding autoradiography, [H-3]MK801 labelling was determ ined at 7, 14, 21, 30 and 60 days after treatment with TMT (single dos e of 8 mg/kg, i.p.) in various hippocampal areas thought to be affecte d by the neurotoxin. At 21-60 days after exposure, a decrease in recep tor binding was observed in CA1 hippocampal subfield (10-20%, P < 0.05 ). A reduction in binding density also occurred in CA4/CA3c, where lab elling vanished completely at longer times. In the molecular layer (ML ) of the dentate gyrus (DG), however, 16-37% (P < 0.05) increase in re ceptor binding was found at 14-60 days postexposure. These results sug gest that exposure to TMT leads to an altered topography of NMDA recep tor density sites in the rat hippocampus. Dynamics of the reduction in receptor binding in CA4/CA3c and CA1 followed the development of the well-known degenerative effects induced by the neurotoxin. in contrast , the enhanced binding density in the ML of the DG may be a part of a mechanism of plastic response of granule cells to denervation/reinnerv ation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.