Arachidonic acid and its metabolites are involved in the expression of morphine dependence in guinea-pig isolated ileum.
The effects of phospholipase A2, cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase inhibitors were investigated on the naloxone-precipitated withdrawal contracture of the acute morphine-dependent guinea-pig ileum in vitro. Mepacrine (a phospholipase A2 inhibitor), tolmetin (selective cyclooxygenase-1 inhibitor) and meloxicam (selective cyclooxygenase-2 inhibitor) treatment before or after morphine was able to both prevent and reverse the naloxone-induced contracture after exposure to morphine in a concentration-dependent fashion. Also, nordihydroguaiaretic acid (5-lipooxygenase inhibitor) was able to block the naloxone-induced contracture following exposure to morphine when injected before or after the opioid agonist. The results of the present study suggest that arachidonic acid and its metabolites (prostaglandins and leukotrienes) are involved in the development of opioid withdrawal.
Capasso
A
A
Department of Pharmaceutical Sciences, University of Salerno, Penta di Fisciano, Italy.
Sorrentino
L
L
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism* / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D000077239:Meloxicam; D009020:Morphine; D009119:Muscle Contraction / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014046:Tolmetin / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D009292:Narcotic Antagonists; D013843:Thiazines; D013844:Thiazoles; D016718:Arachidonic Acid; D009270:Naloxone; D009020:Morphine; D009637:Masoprocol; D014046:Tolmetin; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D000077239:Meloxicam