Ukai M, Shinkai N, Kameyama T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Eur J Pharmacol. 1995 Aug 4;281(2):173-8. doi: 10.1016/0014-2999(95)00239-h.
We investigated the effects of kappa-opioid receptor agonists such as dynorphin A-(1-13) and U-50,488H on the muscarinic M1-selective receptor antagonist pirenzepine (3 micrograms, i.c.v.)-induced impairment of spontaneous alternation performance in the mouse. Although dynorphin A-(1-13)(1-5.6 micrograms, i.c.v.) or U-50,488H ((+/-)trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide, methanesulfonate hydrate) (0.1-1 mg/kg, i.p.) alone did not influence either spontaneous alternation performance or total arm entries, pirenzepine (3 micrograms, i.c.v.) impaired spontaneous alternation performance without producing any significant change in total arm entries. In contrast, dynorphin A-(1-13) (3 and 5.6 micrograms, i.c.v.) and U-50,488H (0.3 and 1 mg/kg, i.p.) ameliorated the pirenzepine (3 micrograms, i.c.v.)-induced impairment of spontaneous alternation performance. The ameliorating effects of dynorphin A-(1-13)(3 micrograms, i.c.v.) and U-50,488H (0.3 mg/kg, i.p.) were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-opioid receptor antagonist. These results suggest that the stimulation of kappa-opioid receptors improves memory dysfunctions resulting from the blockade of muscarinic M1 receptors.
我们研究了强啡肽A-（1-13）和U-50,488H等κ-阿片受体激动剂对毒蕈碱M1选择性受体拮抗剂哌仑西平（3微克，脑室内注射）诱导的小鼠自发交替行为损伤的影响。尽管单独给予强啡肽A-（1-13）（1-5.6微克，脑室内注射）或U-50,488H（（±）反式-3,4-二氯-N-甲基-N-[2-（1-吡咯烷基）-环己基]-苯乙酰胺，甲磺酸盐一水合物）（0.1-1毫克/千克，腹腔注射）对自发交替行为或总臂进入次数均无影响，但哌仑西平（3微克，脑室内注射）会损害自发交替行为，而总臂进入次数没有任何显著变化。相比之下，强啡肽A-（1-13）（3和5.6微克，脑室内注射）和U-50,488H（0.3和1毫克/千克，腹腔注射）可改善哌仑西平（3微克，脑室内注射）诱导的自发交替行为损伤。κ-阿片受体拮抗剂去甲二丙诺啡（4微克，脑室内注射）预处理几乎完全逆转了强啡肽A-（1-13）（3微克，脑室内注射）和U-50,488H（0.3毫克/千克，腹腔注射）的改善作用。这些结果表明，κ-阿片受体的刺激可改善因毒蕈碱M1受体阻断而导致的记忆功能障碍。
