No abstract

The localization of metabotropic glutamate receptors (mGluRs) during development has been associated with brain maturation and plasticity. The developmental immunohistochemical analysis of mGluR1α, mGluR2/3 and mGluR4a expression was performed in the cerebral cortex, hippocampus and basal ganglia at postnatal days (P) 4, 8, 12, 35 and 60. In early stages (P4 and P8) mGluR1α-like immunoreactivity (mGluR1α-LI) was detected in cell bodies and fibers of the frontal cortex, hippocampus and globus pallidus. At P35 and P60, the staining was observed in pyramidal cells and fibers in the deepest layers of the cortex and in stratum oriens of the hippocampus, while a lower labeling was observed in fibers of the globus pallidus. No immunostaining was observed in substantia nigra pars reticulata until P12, when a dense network of fiber staining was detected through the adult stages (P35, P60). mGluR2/3-LI was present from the second week of development in fibers and cell bodies of the stratum lacunosum moleculare of the CA1–CA3 and striatum; this staining pattern persisted until adult stages. mGluR4a-LI was observed at P12 in neuronal bodies of the cortex, in pyramidal cells of the hippocampus and in neuronal cells of the striatum. At P35 and P60, a strong signal was observed in a reduced number of labeled cells of the cerebral cortex, in fibers of the stratum oriens of CA1 and in long processes of substantia nigra pars reticulata. Our results indicate that there are significant changes in the protein expression of mGluR subunits through postnatal development. These differences may play a significant role in the establishment of proper synaptic circuitry in early postnatal life, as well as contributing to the maintenance, stabilization, and plasticity of the rat forebrain, particularly through the participation of mGluR1α and mGluR4a.

The D4 receptor (D4R), a member of the dopamine D2-like receptor family, has been implicated in the pathophysiology of several diseases and has been the target of various investigations regarding its distribution and quantification. The brain distribution of the D4R has been well described in various species, but the quantification is still an issue of controversy, because no specific ligand is commercially available. To circumvent this difficulty we have performed a biochemical and autoradiographical study in brain samples obtained from mice lacking D4Rs and their wild-type siblings; comparison of their binding parameters allows a more accurate quantification of the members of the D2-like receptor family (D2, D3, and D4 receptors). We found that the distribution of D2-like receptors in mouse brain is similar to that of rat brain, i.e., caudate putamen, nucleus accumbens, olfactory tubercle, and hippocampus. The contribution of the D4R to the overall population of D2-like receptors is 17% in nucleus accumbens, 21% in caudate putamen and olfactory tubercle, and 40% in hippocampus. Based on our study we conclude that nemonapride probably binds to nondopaminergic sites that if not properly blocked may lead to overestimations of D4R levels. We observed that the experimental condition that better estimates the density of D4 receptors is the displacement of D2 and D3 [3H]nemonapride binding sites with cold raclopride.