Immunohistochemical distribution of NTS2 neurotensin receptors in the rat central nervous system.

In the present study, we localized the levocabastine-sensitive neurotensin receptor (NTS2) protein in adult rat brain by using an N-terminally-directed antibody. NTS2-like immunoreactivity was broadly distributed throughout the rat brain. At the cellular level, the reaction product was exclusively associated with neurons and predominantly, although not exclusively, with their dendritic arbors. No NTS2 signal was observed over astrocytes, as confirmed by dual confocal microscopic immunofluorescence studies using the astrocytic marker S100beta. High densities of NTS2-like immunoreactive nerve cell bodies and/or processes were detected in many regions documented to receive a dense neurotensinergic innervation, such as the olfactory bulb, bed nucleus of the stria terminalis, magnocellular preoptic nucleus, amygdaloid complex, anterodorsal thalamic nucleus, substantia nigra, ventral tegmental area, and several brainstem nuclei. Most conspicuous among the latter were structures implicated in the descending control of nociceptive inputs (e.g., the periaqueductal gray, dorsal raphe, gigantocellular reticular nucleus, pars alpha, lateral paragigantocellular, and raphe magnus), in keeping with the postulated role of NTS2 receptors in the mediation of neurotensin's supraspinal antinociceptive actions. However, the distribution of NTS2-like immunoreactivity largely exceeded that of neurotensin terminal fields, and some of the highest concentrations of the receptor were found in areas devoid of neurotensinergic inputs such as the cerebral cortex, the hippocampus, and the cerebellum, suggesting that neurotensin may not be the exclusive endogenous ligand for this receptor subtype.