[H-3]1,3-di(2-tolyl)guanidine and [H-3](+)pentazocine binding sites in the rat brain: Autoradiographic visualization of the putative sigma(1) and sigma(2) receptor subtypes

Sigma (sigma) receptors have generated a great deal of interest on the basis of their possible role in psychosis and on locomotor behaviors. The effects of sigma drugs on these various functions are apparently mediated by different sigma receptor subtypes (sigma(1) and sigma(2)). However, little information is currently available on the discrete anatomical distribution of these putative sigma receptor subtypes in the rat brain. The aim of the present study was to investigate, by quantitative autoradiography, the respective distribution of purported sigma(1) and sigma(2) receptor subtypes in the rat brain using [H-3]1,3-di(2-tolyl)guanidine, a universal sigma ligand, (86) and [H-3](+)pentazocine, a selective sigma(1) ligand.(7) Putative sigma(2) receptor sites were visualized using [H-3]1,3-di(2-tolyl)guanidine in presence of a saturating concentration of (+)pentazocine. Specific [H-3]1,3-di(tolyl)guanidine and [H-3](+)pentazocine binding sites were found to be widely but discretely distributed in the rat brain. The highest densities of specific labeling were seen in various cranial nerve nuclei, followed by certain hippocampal sub-fields and laminae, the red nucleus, the interpeduncular nucleus and mid-layers of primary and secondary motor cortices. Lower amounts of specific binding were present in various other structures including most thalamic and hypothalamic nuclei, and the cerebellum Interestingly, [H-3]1,3-di(2-tolyl)guanidine binding in the motor cortex was found to be particularly resistant to a saturating concentration of (+)pentazocine suggesting an enrichment in the putative sigma(2) receptor subtype. This also applies for a few other structures such as the nucleus accumbens, substantia nigra pars reticulata, central gray matter, occulomotor nucleus and cerebellum On the other hand, the sigma(1) subtype is more abundant in most other regions with the highest densities seen in the dentate gyrus of the hippocampal formation, facial nucleus, and various thalamic and hypothalamic nuclei. The comparative localization of the sigma(1) and sigma(2) receptor binding sites probably relates to the differential effects of sigma(1) and sigma(2) drugs in the rat brain. Copyright (C) 1996 IBRO.