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Sigma receptor ligands attenuate methamphetamine‐induced hyperthermia but do not modulate IL‐1B mRNA expression in select brain regions

Methamphetamine is one of the most widely abused drugs worldwide, with hyperthermia being a primary cause of death. Methamphetamine‐induced hyperthermia involves a variety of cellular mechanisms, including increases in IL‐1β. Previous studies indicate methamphetamine interacts with sigma receptors and selective sigma receptor ligands attenuate some of the effects of methamphetamine, including hyperthermia. The purpose of the current study was to determine if sigma receptor ligands can attenuate acute increases in body temperature following methamphetamine administration and whether these protective effects occur through modulation of IL‐1β. To evaluate the role of sigma receptors, male, Swiss Webster mice were pretreated with AZ66 or SN79 15 min prior to an acute bolus dose of methamphetamine and body temperatures were recorded for up to 45 min. Acute, bolus administration of methamphetamine caused a significant, dose dependent increase in body temperature, and pretreatment with each of the sigma receptor ligands significantly attenuated methamphetamine‐induced hyperthermia. To determine if these protective effects were related to the modulation of IL‐1β, the mouse striatum, cortex and hypothalamus were collected 45 min after drug administration and evaluated for IL‐1β mRNA expression. Methamphetamine produced a significant increase in IL‐1β mRNA in each of these brain regions; however, sigma receptor ligands failed to attenuate the changes in IL‐1β mRNA expression. It appears that sigma ligands can mitigate methamphetamine‐induced hyperthermia through a different mechanism from that involved in the modulation of IL‐1β mRNA expression. (Supported by NIDA DA013978, DA023205)