The role of the NO/NMDA pathways in the development of morphine withdrawal induced by naloxone in vitro.
The effect of nitric oxide (NO)/N-methyl-d-aspartate (NMDA) pathways on naloxone-induced withdrawal contracture was studied in vitro in a model of acute morphine dependence in the isolated guinea pig ileum. Exposure of the isolated guinea pig ileum to morphine (10(-5) M) for 5 min resulted in acute dependence, characterized by a strong withdrawal contracture induced by naloxone (5x10(-5) M). The NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 5x10(-4) M) as well as the soluble guanylate cyclase inhibitor methylene blue (MB; 10 microM) were found to significantly attenuate the naloxone-induced withdrawal contracture. In addition, the NO precursor L-arginine (5x10(-4) M) as well as the NO donors sodium nitroprusside (SNP; 1 microM) and sodium azide (NaZ; 10 microM) were able to revert the effect of L-NAME returning the amplitude of naloxone-induced contracture to the same level in control morphine-dependent ilea. We also demonstrated that the competitive NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5; 50 microM) potently reduced the amplitude of naloxone-induced contracture in the same model, an effect that was reversed by co-administration of the excitatory amino acid L-glutamate (40 microM). This in vitro study confirms the implication of the NO/NMDA pathways in morphine dependence.
Gabra
Bichoy H
BH
Institute of Pharmacology of Sherbrooke, School of Medicine, University of Sherbrooke 3001, 12E Avenue Nord, Sherbrooke, Que., Canada J1H5N4. Bichoy.Gabra@USherbrooke.ca
Afify
Elham A
EA
Daabees
Tahia T
TT
Abou Zeit-Har
Mohamed S
MS
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009021:Morphine Dependence / Q000503:physiopathology*; D016202:N-Methylaspartate / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D009569:Nitric Oxide; D009270:Naloxone; D016202:N-Methylaspartate