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Published on: July 29, 2014
Effect of NMDA receptor antagonist on naloxone-precipitated withdrawal signs in cholestatic mice
Ahmad Reza Dehpour1, Morteza Samini, Hossein Rastegar
1Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
The ability of NMDA antagonist MK-801 to block the expression of opioid-like withdrawal signs was examined in bile duct-ligated mice and the signs were compared with sham operated and unoperated animals. Administration of MK-801 (0/1 mg/kg), 10 min prior to naloxone challenge, significantly reduced the investigated withdrawal signs (jumping, diarrhoea, grooming and climbing) in bile duct-ligated animals. Chronic administration (five consecutive days) of MK-801 (0/1 mg/kg) also decreased all the withdrawal signs in the experimental animals. In an independent series of experiments, the effect of acute and chronic administration of MK-801 on tail-flick latency was investigated in bile duct-ligated animals. Pretreatment with the drug significantly decreased the antinociception induced by bile duct ligation in the mice. The results of this study support evidence for the involvement of the NMDA receptor in yopioidergic-dependent manifestations in a model of obstructive cholestasis. Copyright 2000 John Wiley & Sons, Ltd.
Insights
The NMDA antagonist MK-801 effectively reduced opioid-like withdrawal signs in mice with bile duct ligation. This suggests the N-methyl-D-aspartate (NMDA) receptor plays a role in opioid withdrawal during cholestasis.
Area of Science:
- Neuropharmacology
- Gastroenterology
- Pain research
Background:
- Obstructive cholestasis can induce opioid-like withdrawal symptoms.
- The role of N-methyl-D-aspartate (NMDA) receptors in these withdrawal manifestations is not fully understood.
Purpose of the Study:
- To investigate the efficacy of the NMDA antagonist MK-801 in blocking opioid-like withdrawal signs.
- To examine the effect of MK-801 on antinociception in a mouse model of obstructive cholestasis.
Main Methods:
- Bile duct ligation was performed on mice to induce cholestasis.
- MK-801 was administered acutely and chronically prior to naloxone challenge.
- Withdrawal signs (jumping, diarrhea, grooming, climbing) and tail-flick latency were measured.
Main Results:
- Acute and chronic administration of MK-801 significantly reduced opioid-like withdrawal signs in bile duct-ligated mice.
- MK-801 pretreatment decreased the antinociception observed in bile duct-ligated animals.
- MK-801 administration also affected tail-flick latency.
Conclusions:
- The N-methyl-D-aspartate (NMDA) receptor is implicated in opioid-dependent withdrawal symptoms during obstructive cholestasis.
- NMDA receptor antagonism may represent a therapeutic target for managing withdrawal in cholestatic conditions.
