The σ-1 receptor is an endoplasmic reticulum (ER) chaperone that stabilizes the type 3 inositol triphosphate (IP3) receptors. The IP3 receptors reside at the ER-mitochondrial interface and thereby regulate intracellular calcium signaling. Methamphetamine binds the σ-1 receptor and can cause cytotoxicity at high doses. In this issue, Hayashi et al. describe the effect of methamphetamine exposure on expression and localization of the σ-1 receptor in the rat brain. It was found that both passive and self-administered methamphetamine increased σ-1 expression in the ventral tegmental area and substantia nigra indicative of ER stress. However, it was found that σ-1 expression was substantially elevated in the olfactory bulb, only in rats that self-administered methamphetamine, and that it was colocalized with dopamine D1 receptors. These observations suggest a key role for the D1 and σ-1 receptors in the olfactory bulb in addictive behavior.
See article at J Pharmacol Exp Ther 2010, 332:1054–1063.
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