Comparison of the effects of specific and nonspecific inhibition of nitric oxide synthase on morphine analgesia, tolerance and dependence in mice.
The effects of L-Canavanine, a selective inducible nitric oxide synthase (NOS) inhibitor and N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor, on pain threshold and morphine induced analgesia, tolerance and dependence in mice were investigated and compared. Morphine was administered by subcutaneous implantation of a pellet containing 40 mg free base and withdrawal was precipitated by intraperitoneal (i.p.) injection of naloxone (2 mg/kg). L-Canavanine (200 mg/kg, i.p.) did not affect the pain threshold, morphine-induced analgesia and the induction and expression phases of morphine tolerance and dependence. L-NAME (20 mg/kg, i.p.) significantly (p < 0.05) enhanced the pain threshold, potentiated morphine-induced analgesia and attenuated the expression phase of morphine dependence which has been characterized by withdrawal signs and body weight loss, but did not modify the induction phase of morphine tolerance and dependence. It is concluded that constitutive NOS isoforms which were inhibited by L-NAME may be involved specifically in the mechanisms of morphine induced analgesia, tolerance and dependence.
Ozek
Mehmet
M
Department of Pharmacology and Clinical Pharmacology, Istanbul University, Istanbul Faculty of Medicine, Capa, Turkey.
Uresin
Yağiz
Y
Güngör
Mehmet
M
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002172:Canavanine / Q000494:pharmacology; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000523:psychology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D010147:Pain Measurement / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D015431:Weight Loss / Q000187:drug effects
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D002172:Canavanine; D009020:Morphine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019331:NG-Nitroarginine Methyl Ester