Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus.

Abstract

Methamphetamine is currently one of the most widely abused drugs worldwide, with hyperthermia being a leading cause of death in methamphetamine overdose situations. Methamphetamine-induced hyperthermia involves a variety of cellular mechanisms, including increases in hypothalamic interleukin-1 beta (IL-1β) expression. Methamphetamine also interacts with sigma receptors and previous studies have shown that sigma receptor antagonists mitigate many of the behavioral and physiological effects of methamphetamine, including hyperthermia. The purpose of the current study was to determine if the attenuation of methamphetamine-induced hyperthermia by the sigma receptor antagonists, AZ66 and SN79, is associated with a concomitant attenuation of IL-1β mRNA expression, particularly in the hypothalamus. Methamphetamine produced dose- and time-dependent increases in core body temperature and IL-1β mRNA expression in the hypothalamus, striatum, and cortex in male, Swiss Webster mice. Pretreatment with the sigma receptor antagonists, AZ66 and SN79, significantly attenuated methamphetamine-induced hyperthermia, but further potentiated IL-1β mRNA in the mouse hypothalamus when compared to animals treated with methamphetamine alone. These findings suggest sigma receptor antagonists attenuate methamphetamine-induced hyperthermia through a different mechanism from that involved in the modulation of hypothalamic IL-1β mRNA expression.

• Authors: Michael J Seminerio, Matthew J Robson, Christopher R McCurdy, Rae R Matsumoto
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 691 Issue 1-3 Pg. 103-9 (Sep 15 2012) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 22820108 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-1beta
• Neurotoxins
• Piperazines
• RNA, Messenger
• Receptors, sigma
• Methamphetamine

Topics

• Animals
• Body Temperature (drug effects)
• Dose-Response Relationship, Drug
• Fever (chemically induced, drug therapy, genetics, physiopathology)
• Gene Expression Regulation (drug effects)
• Hypothalamus (drug effects, metabolism, physiopathology)
• Interleukin-1beta (genetics)
• Male
• Methamphetamine (toxicity)
• Mice
• Neurotoxins (toxicity)
• Piperazines (chemistry, pharmacology, therapeutic use)
• RNA, Messenger (genetics, metabolism)
• Receptors, sigma (antagonists & inhibitors)
• Reproducibility of Results
• Time Factors