Potentiation of Delta(9)-tetrahydrocannabinol-induced analgesia by morphine in mice: Involvement of mu- and kappa-opioid receptors

被引:78
作者
Reche, I [1 ]
Fuentes, JA [1 ]
RuizGayo, M [1 ]
机构
[1] UNIV COMPLUTENSE MADRID,FAC FARM,DEPT FARMACOL,E-28040 MADRID,SPAIN
关键词
analgesia; morphine; opioid; Delta(9)-tetrahydrocannabinol; SR-141,716 A; dynorphin; nor-binaltorphimine; beta-funaltrexamine; DAMGO; ([D-Ala(2); N-Me-Phe(4); Gly-ol(5)]enkephalin);
D O I
10.1016/S0014-2999(96)00752-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The antinociceptive effect of peripheral Delta(9)-tetrahydrocannabinol was examined in mice previously treated with an inactive dose of morphine. The ED(50) of Delta(9)-tetrahydrocannabinol was significantly reduced by morphine, both in the tail-flick test (0.85 vs. 2.10 mg/kg) and in the hot-plate test (1.51 vs. 4.71 mg/kg and 0.73 vs. 2.47 mg/kg in jumping and paw-lick responses, respectively). The synergistic effect between morphine and Delta(9)-tetrahydrocannabinol was partially blocked by the cannabinoid receptor antagonist, SR-141,716 A [(N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichorophenyl)-4-methyl-3-pyrazolecarboxamide, hydrochloride)]: at a dose of 2 mg/kg (i.p.) as well as by the opioid receptor antagonist naloxone, at the dose of 1 mg/kg (s.c.). Such an effect was also blocked by i.t. nor-binaltorphimine (a kappa-selective opioid receptor antagonist) given at 20 mu g/mouse as well as by beta-funaltrexamine (a mu-selective opioid receptor antagonist) at a dose of 2 nmol/mouse (i.c.v., 24 h before the test). Accordingly, the mu-opioid receptor agonist DAMGO ([D-Ala(2), N-Me-Phe(4),Gly-ol(5)]enkephalin) potentiated the effect of Delta(9)-tetrahydrocannabinol. These data show that the synergism between morphine and Delta(9)-tetrahydrocannabinol appears to involve cannabinoid as well as mu-supraspinal and kappa-spinal opioid receptors.
引用
收藏
页码:11 / 16
页数:6
相关论文
共 27 条
  • [1] ANTIDEPRESSANT-TYPE EFFECTS OF ENDOGENOUS ENKEPHALINS PROTECTED BY SYSTEMIC RB-101 ARE MEDIATED BY OPIOID-DELTA AND DOPAMINE-D1 RECEPTOR STIMULATION
    BAAMONDE, A
    DAUGE, V
    RUIZGAYO, M
    FULGA, IG
    TURCAUD, S
    FOURNIEZALUSKI, MC
    ROQUES, BP
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 216 (02) : 157 - 166
  • [2] INHIBITION OF NALOXONE-INDUCED WITHDRAWAL IN MORPHINE-DEPENDENT MICE BY "L-TRANS-DELTA9-TETRAHYDROCANNABINOL
    BHARGAVA, HN
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1976, 36 (01) : 259 - 262
  • [3] BHARGAVA HN, 1976, PSYCHOPHARMACOLOGY, V49, P267, DOI 10.1007/BF00426828
  • [4] BLOOM AS, 1977, J PHARMACOL EXP THER, V200, P263
  • [5] D'amour FE, 1941, J PHARMACOL EXP THER, V72, P74
  • [6] ISOLATION AND STRUCTURE OF A BRAIN CONSTITUENT THAT BINDS TO THE CANNABINOID RECEPTOR
    DEVANE, WA
    HANUS, L
    BREUER, A
    PERTWEE, RG
    STEVENSON, LA
    GRIFFIN, G
    GIBSON, D
    MANDELBAUM, A
    ETINGER, A
    MECHOULAM, R
    [J]. SCIENCE, 1992, 258 (5090) : 1946 - 1949
  • [7] DEWEY WL, 1986, PHARMACOL REV, V38, P151
  • [8] FORMATION AND INACTIVATION OF ENDOGENOUS CANNABINOID ANANDAMIDE IN CENTRAL NEURONS
    DIMARZO, V
    FONTANA, A
    CADAS, H
    SCHINELLI, S
    CIMINO, G
    SCHWARTZ, JC
    PIOMELLI, D
    [J]. NATURE, 1994, 372 (6507) : 686 - 691
  • [9] EDDY NB, 1953, J PHARMACOL EXP THER, V107, P385
  • [10] FUJIMOTO JM, 1990, J PHARMACOL EXP THER, V254, P1