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

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: Matthew J Robson, Michael J Seminerio, Christopher R McCurdy, Andrew Coop, Rae R Matsumoto
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 65 Issue 2 Pg. 343-9 ( 2013) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 23744418 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 3-(4-(4-cyclohexylpiperazine-1-yl)pentyl)-6-fluorobenzo(d)thiazole-2(3H)-one
• Benzothiazoles
• Dopamine Agents
• N-phenethylpiperidine oxalate
• Oxalates
• Piperazines
• Piperidines
• Receptors, sigma
• Methamphetamine
• Dopamine

Topics

• Animals
• Benzothiazoles (pharmacology)
• Body Temperature (drug effects)
• Corpus Striatum (drug effects, metabolism)
• Dopamine (metabolism)
• Dopamine Agents (toxicity)
• Fever (chemically induced, prevention & control)
• Male
• Methamphetamine (toxicity)
• Mice
• Neurotoxicity Syndromes (etiology, prevention & control)
• Oxalates (pharmacology)
• Piperazines (pharmacology)
• Piperidines (pharmacology)
• Receptors, sigma (antagonists & inhibitors)