Age-related differences in NMDA/metabotropic glutamate receptor binding in rat substantia nigra

Both N-methyl-D-aspartate (NMDA) and quisqualate/AMPA-insensitive metabotropic glutamate (mGlu) receptors mediate glutamate neurotransmission in substantia nigra (SN). In this work, NMDA and mGlu receptor sites in substantia nigra pars compacta (SNC) and pars reticulata were autoradiographically mapped in rat brains using specific binding of (+)³H-MK801 or ³H-glutamate, with saturating concentrations of NMDA, AMPA and quisqualate. In brains of both adult and postnatal day 15 (PN15) male rats, prepared at subjective mid-day of a 12h light/12h dark (12h L/12h D) cycle, specific binding at NMDA and mGlu sites in substantia nigra was pronounced when compared with control binding. The (+)³H-MK801 binding in adults was spatially heterogeneous. Overall binding density in pars compacta was higher relative to binding density in pars reticulata with a mean percent change (Δx̄%) of 32%. Within the pars reticulata but not pars compacta, there were rostro-caudal differences with considerably denser binding in the posterior compared with the anterior pars reticulata (Δx̄%=108%). PN15 rats showed a less pronounced heterogeneity in pars compacta versus pars reticulata binding, (Δx̄%=27%), and less rostro-caudal differentiation in (+)³H-MK801 binding density throughout pars reticulata (Δx̄%=46%). ³H-glutamate binding in both adult and PN15 rats was less dense overall than (+)³H-MK801 binding. In adults, there was no difference in binding density between pars compacta and pars reticulata (Δx̄%=0.4%), but there were marked heterogeneities when binding was compared between anterior versus posterior pars compacta (Δx̄%=29%), and anterior versus posterior pars reticulata (Δx̄%=25%). This rostro-caudal heterogeneity in ³H-glutamate binding density was also present in PN15 pars compacta (Δx̄%=45%) but not in pars reticulata. Our findings mirror similar anterior/posterior heterogeneities in the GABAergic system in adult and PN15 male rats and may reflect a developmental change in both the structure and anticonvulsant/proconvulsant properties of substantia nigra pars reticulata (SNR) with age.