σ Receptor antagonist attenuation of methamphetamine-induced neurotoxicity is correlated to body temperature modulation.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 2
Abstract
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 METH-induced 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.
Authors and Affiliations
Matthew Robson, Michael Seminerio, Christopher McCurdy, Andrew Coop, Rae Matsumoto
Keywords
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