Spatiotemporal changes in hippocampal NMDA receptor binding as a consequence of trimethyltin neurotoxicity in the rat

Abstract

In the present study we examined the presumable changes in the distribution of N-methyl- d-aspartate (NMDA) receptors in the hippocampus of rat exposed to a potent neurotoxic drug, trimethyltin (TMT). Using in vitro receptor binding autoradiography, [ 3H]MK801 labelling was determined at 7, 14, 21, 30 and 60 days after treatment with TMT (single dose of 8 mg/kg, i.p.) in various hippocampal areas thought to be affected by the neurotoxin. At 21–60 days after exposure, a decrease in receptor binding was observed in CA1 hippocampal subfield (10–20%, P<0.05). A reduction in binding density also occurred in CA4/CA3c, where labelling vanished completely at longer times. In the molecular layer (ML) of the dentate gyrus (DG), however, 16–37% ( P<0.05) increase in receptor binding was found at 14–60 days postexposure. These results suggest that exposure to TMT leads to an altered topography of NMDA receptor 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/reinnervation.