DIFFERENTIAL-EFFECTS OF SYSTEMICALLY ADMINISTERED NOR-BINALTORPHIMINE (NOR-BNI) ON KAPPA-OPIOID AGONISTS IN THE MOUSE WRITHING ASSAY

被引:130
作者
BROADBEAR, JH
NEGUS, SS
BUTELMAN, ER
DECOSTA, BR
WOODS, JH
机构
[1] UNIV MICHIGAN, DEPT PSYCHOL, ANN ARBOR, MI 48109 USA
[2] NIDDK, BETHESDA, MD 20892 USA
关键词
NOR-BINALTORPHIMINE; CI-977; U69,593; U50,488; BREMAZOCINE; ETHYLKETOCYCLAZOCINE; MR2034; MORPHINE; BW-373U86; BETA-FUNALTREXAMINE; KAPPA ANTAGONISTS; ACETIC ACID-INDUCED WRITHING; MICE;
D O I
10.1007/BF02245071
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The opioid antagonist effects of systemically administered nor-binaltorphimine (nor-BNI) were evaluated against the kappa agonists CI-977, U69,593, U50,488, ethylketocyclazocine (EKC), Mr2034 and bremazocine, the mu agonist morphine and the alkaloid delta agonist BW-373U86 in the acetic acid-induced writhing assay in mice. All eight agonists completely and dose-dependently inhibited writhing. Antagonism of CI-977 was apparent 1 h after administration of 32 mg/kg nor-BNI, peaking after 4 h and was maintained for at least 4 weeks; no antagonist effects of nor-BNI were apparent after 8 weeks. Nor-BNI (32 mg/kg) caused little or no antagonism of morphine or BW-373U86 at 1 h and none at 24 h after nor-BNI administration. Subsequently, dose-effect curves for CI-977, U50,488, U69,593, EKC, Mr2034 and bremazocine were determined 24 h after pretreatment with 3.2, 10 and 32 mg/kg nor-BNI. Pretreatment with 3.2 mg/kg nor-BNI produced significant antagonism of all six kappa agonists, suggesting that their antinociceptive effects were mediated at least in part by nor-BNI-sensitive kappa receptors. At higher doses, nor-BNI dose-dependently shifted the agonist dose-effect curves of CI-977, U50,488, U69,593 and bremazocine, but not those of EKC and Mr2034, suggesting that the latter compounds may be producing effects via nor-BNI-insensitive receptors. Mu receptor involvement was demonstrated following a 24 h pretreatment with 32 mg/kg beta-FNA in combination with nor-BNI, which significantly increased the degree of antagonism of Mr2034 and EKC from that seen with nor-BNI alone. Hence, SC administered nor-BNI selectively antagonized agonist activity mediated through kappa-opioid receptors without differentiating between kappa subtypes. Nor-BNI also enabled the mu agonist activity of proposed kappa agonists to be measured.
引用
收藏
页码:311 / 319
页数:9
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