QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.107.129973v1 323/3/990    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Benamar, K. Articles by Adler, M. W. Search for Related Content PubMed PubMed Citation Articles by Benamar, K. Articles by Adler, M. W.

NEUROPHARMACOLOGY

Deletion of µ-Opioid Receptor in Mice Alters the Development of Acute Neuroinflammation

Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania

The realization that the µ-opioid system plays a key role in the control of the process of neuroinflammation is a new concept that may lead to identification of novel therapies for this extremely widespread and intractable syndrome. Fever is the hallmark among the defense mechanisms evoked by the entry into the body of pathogens to initiate the innate immune responses. In an attempt to determine the possible involvement of µ-opioid receptors in the control of brain inflammation, we examined the effect of their deletion on the fever induced by i.c.v. injection of lipopolysaccharide (LPS). The first series of experiments examined the thermal consequence of the absence of µ-opioid receptors on circadian body temperature rhythm and basal body temperature. µ-Opioid receptor knockout mice (MOP-KO) showed a normal circadian body temperature rhythm and basal body temperature compared with the wild type (WT). The second series of experiments investigated i.c.v. administration of LPS on body temperature in WT and MOP-KO. In the WT, i.c.v. injection of 100 ng of LPS induced fever, but there was no increase in body temperature in the MOP-KO mice. Saline, given i.c.v., did not alter the body temperature, either in WT or MOP-KO. These results show that the µ-opioid system participates in the control of acute neuroinflammation, further reinforcing our earlier finding that the opioid system is involved in the pathogenesis of fever induced by bacterial LPS, and that µ-opioid receptors are the target for morphine-induced hyperthermia.

Address correspondence to: Dr. Khalid Benamar, Center of Substance Abuse Research, Temple University School of Medicine, 3400 N. Broad St., Philadelphia, PA 19140. E-mail: kbenamar{at}temple.edu