Comparison of the effects of specific and nonspecific inhibition of nitric oxide synthase on morphine analgesia, tolerance and dependence in mice

被引:48
作者
Özek, M [1 ]
Üresin, Y [1 ]
Güngör, M [1 ]
机构
[1] Univ Istanbul, Fac Med, Dept Pharmacol & Clin Pharmacol, TR-34390 Istanbul, Turkey
关键词
morphine; analgesia; dependence; tolerance; nitric oxide synthase (NOS); L-Canavanine; L-NAME;
D O I
10.1016/S0024-3205(03)00100-0
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The effects of L-Canavanine, a selective inducible nitric oxide synthase (NOS) inhibitor and N-G-nitro-Larginine 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. (C) 2003 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:1943 / 1951
页数:9
相关论文
共 33 条
[1]  
ADAMS ML, 1993, LIFE SCI, V52, P245
[2]  
Allen RM, 2000, J PHARMACOL EXP THER, V295, P1012
[3]   NITRIC-OXIDE MEDIATES GLUTAMATE-LINKED ENHANCEMENT OF CGMP LEVELS IN THE CEREBELLUM [J].
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (22) :9030-9033
[4]  
CURTIS DR, 1965, PHARMACOL REV, V17, P347
[5]   Role of nitric oxide in the induction and expression of morphine tolerance and dependence in mice [J].
Dambisya, YM ;
Lee, TL .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (05) :914-918
[6]   NITRIC-OXIDE SIGNALING IN THE CENTRAL-NERVOUS-SYSTEM [J].
GARTHWAITE, J ;
BOULTON, CL .
ANNUAL REVIEW OF PHYSIOLOGY, 1995, 57 :683-706
[7]   GLUTAMATE, NITRIC-OXIDE AND CELL CELL SIGNALING IN THE NERVOUS-SYSTEM [J].
GARTHWAITE, J .
TRENDS IN NEUROSCIENCES, 1991, 14 (02) :60-67
[8]  
Gibson R D, 1970, J Pharm Sci, V59, P426, DOI 10.1002/jps.2600590338
[9]   Decrease of tolerance to, and physical dependence on morphine by, glutamate receptor antagonists [J].
Gonzalez, P ;
Cabello, P ;
Germany, A ;
Norris, B ;
Contreras, E .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 332 (03) :257-262
[10]   ELECTROPHYSIOLOGICAL EVIDENCE FOR A ROLE OF NITRIC-OXIDE IN PROLONGED CHEMICAL NOCICEPTION IN THE RAT [J].
HALEY, JE ;
DICKENSON, AH ;
SCHACHTER, M .
NEUROPHARMACOLOGY, 1992, 31 (03) :251-258