Description) The targeting of opioid receptors, as well as their coordinated interactions with N-methyl-D-aspartate subtype of glutamate receptors (NMDARs), is crucial for normal brain development and motor functions involving patch-matrix compartments in the mammalian caudate-putamen nucleus (CPN). During the critical developmental plasticity period, mu and delta opioid receptors (MOR, DOR) play either complementary or opposite roles that may in part involve functional interaction with NMDAR. The goal of this application is to test the hypothesis that there are age-related differences in the subcellular localization of MOR and/or DOR, which are correlated with synaptogenesis and parallel those of NMDAR in the CPN.
The specific aims i n each of the three proposed studies will be pursued by examining the localization of sequence specific antipeptide antisera against MOR, DOR, or NMDAR in the rat CPN during postnatal ontogeny. The results obtained from these studies will complement and extend previous knowledge that age-dependent MOR and DOR subcellular distributions are functionally linked to neuronal maturation; that developing NMDAR is largely involved in activity-dependent synaptic plasticity and has a subcellular distribution that parallels the distribution of opioid receptors; and that prenatal opioid availability differentially controls the ontogeny of neurons containing opioid and/or glutamate receptors. Understanding opioid and NMDA receptor targeting during development in the rat model may provide information leading to new approaches for reactivation of developmental plasticity in human brain.
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