[3H]1,3-di(2-tolyl)guanidine and [3H](+)pentazocine binding sites in the rat brain: autoradiographic visualization of the putative sigma1 and sigma2 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 (sigma1 and sigma2). 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 sigma1 and sigma2 receptor subtypes in the rat brain using [3H]1,3-di(2-tolyl)guanidine, a universal sigma ligand, and [3H](+)pentazocine, a selective sigma1 ligand. Putative sigma2 receptor sites were visualized using [3H]1,3-di(2-tolyl)guanidine in presence of a saturating concentration of (+)pentazocine. Specific [3H]1,3-di(tolyl)guanidine and [3H](+)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, [3H]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 sigma2 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 sigma1 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 sigma1 and sigma2 receptor binding sites probably relates to the differential effects of sigma1 and sigma2 drugs in the rat brain.