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Updated: May 10, 2026
A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
σ Receptor antagonist attenuation of methamphetamine-induced neurotoxicity is correlated to body temperature
Matthew J Robson1, Michael J Seminerio, Christopher R McCurdy
1Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, 1 Medical Center Drive, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA.
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.
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