Deletion of mu-opioid receptor in mice alters the development of acute neuroinflammation.
The realization that the mu-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 mu-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 mu-opioid receptors on circadian body temperature rhythm and basal body temperature. Mu-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 mu-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 mu-opioid receptors are the target for morphine-induced hyperthermia.
Benamar
Khalid
K
Center of Substance Abuse Research, Temple University School of Medicine, 3400 N. Broad St., Philadelphia, PA 19140, USA. kbenamar@temple.edu
Yondorf
Menachem
M
Barreto
Veronica T
VT
Geller
Ellen B
EB
Adler
Martin W
MW
D000208:Acute Disease; D000818:Animals; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D005334:Fever / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; C404943:Oprm protein, mouse; D017450:Receptors, Opioid, mu