σ Receptor antagonist attenuation of methamphetamine-induced neurotoxicity is correlated to body temperature modulation

Background: methamphetamine (meth) causes hyperthermia and dopaminergic neurotoxicity in the rodent striatum. meth interacts with σ receptors and σ receptor antagonists normally mitigate meth-induced hyperthermia and dopaminergic neurotoxicity. the present study was undertaken because in two experiments,pretreatment with σ receptor antagonists failed to attenuate methinduced hyperthermia in mice. this allowed us to determine whether the ability of σ receptor antagonists (az66 and ac927) to mitigate meth-induced neurotoxicity depends upon their ability to modulate meth-induced hyperthermia. methods: mice were treated using a repeated dosing paradigm and body temperatures recorded. striatal dopamine was measured one week post-treatment. results: the data indicate that the ability of σ receptor antagonists to attenuate meth-induced dopaminergic neurotoxicity is linked to their ability to block meth-induced hyperthermia. conclusion: the ability of σ receptor antagonists to mitigate meth-induced hyperthermia may contribute to its neuroprotective actions. copyright © 2013 by institute of pharmacology.