Naloxone-induced morphine withdrawal increases the number and degranulation of mast cells in the thalamus of the mouse.
Naloxone-induced jumping in morphine-dependent mice is inhibited by cromolyn, a mast cell stabilizer, suggesting that this characteristic withdrawal behavior results from degranulation of mast cells. Because withdrawal is considered as a central phenomenon, degranulation of mast cells located within the CNS may influence aspects of opioid withdrawal. The present study evaluates histologically whether naloxone, injected into opioid dependent mice, induces degranulation of mast cells. Seventy-two hours after the s.c. implantation of a 75 mg morphine pellet, the number and degranulation of thalamic mast cells did not differ from those in placebo-implanted controls. However, two injections of 50 mg/kg of naloxone, 30 and 60 min before tissue collection, increased the number of degranulated mast cells compared to those in mice injected with saline. Analysis throughout the entire thalamus (90 40-micro sections) revealed increases in the total number of mast cells as well as the number that were degranulated, especially in sections 52-60, corresponding to Bregma -2.18 to 2.54. Here, mast cells were clustered in the IGL and VPL/VPM nuclei, and redistributed from the ventromedial to the dorsolateral aspects of the Po and PF nuclei during withdrawal. Degranulation was also greater throughout the LD, LP nuclei during withdrawal. These data reveal a novel neuroimmune reaction to opioid withdrawal in the CNS.
Taiwo
Oludare B
OB
Department of Veterinary Pathobiology, University of Minnesota, Room 295, Animal Science/Veterinary Medicine Building, 1988 Fitch Avenue, St. Paul, MN 55108, USA.
Kovács
Katalin J
KJ
Sperry
Lauren C
LC
Larson
Alice A
AA
D000818:Animals; D002452:Cell Count / Q000379:methods; D015550:Cell Degranulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000473:pathology*; D013788:Thalamus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D009270:Naloxone; D009020:Morphine