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

Robson MJ, Seminerio MJ, McCurdy CR, Coop A, Matsumoto RR
Pharmacol Rep. 2013 65 (2): 343-9

PMID: 23744418 · DOI:10.1016/s1734-1140(13)71009-0

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.

MeSH Terms (15)

Animals Benzothiazoles Body Temperature Corpus Striatum Dopamine Dopamine Agents Fever Male Methamphetamine Mice Neurotoxicity Syndromes Oxalates Piperazines Piperidines Receptors, sigma

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