Interaction of [3H](–)‐SKF‐10,047 with Brain σ Receptors: Characterization and Autoradiographic Visualization

Abstract: The σ opiates differ from other opiates in their stimulatory and psychotomimetic actions. The σ opiate [3H](–)‐SKF‐10,047 has been used to characterize σ receptors in rat nervous tissue. Binding of [3H](–)‐SKF10,047 to rat brain membranes was of high affinity, saturable, and reversible. Scatchard analysis revealed the apparent interaction of this drug with two distinct binding sites characterized by affinities of 0.03 and 75 nM (5 mM Tris‐HCI buffer, pH 7.4, at 4°C). Competition analyses involving rank order determinations for a series of opiates and other drugs indicate that the high‐affinity binding site is the μ opiate receptor. The lower‐affinity site (revealed after suppression of μ and δ receptor binding) has been identified as the σ opiate/phencyclidine receptor. In vitro autoradiography has been used to visualize neuronanatomical patterns of receptors labeled using [3H](–)‐SKF‐10,047 in the presence of normorphine and [D‐Ala2,D‐Leu5]enkephalin to block μ and δ interactions, respectively. Labeling patterns differ markedly from those for μ, δ, or K receptors. The highest densities (determined by quantitative autoradiography) are found in the medial portion of the nucleus accumbens, amygdaloid nucleus, hippocampal formation, central gray, locus coeruleus, and the parabrachial nuclei, Receptors in these structures could account for the stimulatory, mood‐altering, and analgesic properties of the σ opiates. Although not the most selective σ opiate ligand, [3H](–)‐SKF‐10,047 binds to σ opiate receptors in brain, and this interaction can be readily distinguished from its interactions with other classes of brain opiate receptors.