Suzuki T, Yoshiike M, Mizoguchi H, Kamei J, Misawa M, Nagase H
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Jpn J Pharmacol. 1994 Sep;66(1):131-7. doi: 10.1254/jjp.66.131.
Effects of highly selective delta-opioid receptor antagonists on the morphine-induced place preference in ddY and mu 1-opioid receptor deficient CXBK mice were investigated. Pretreatment with naltrindole (NTI: a non-selective delta-opioid receptor antagonist), 7-benzylidenenaltrexone (BNTX: a selective delta 1-opioid receptor antagonist) or naltriben (NTB: a selective delta 2-opioid receptor antagonist) abolished the morphine-induced place preference in ddY mice in a dose-dependent manner. These findings suggest that the morphine-induced place preference may be mediated by both delta 1- and delta 2-opioid receptors. On the other hand, in mu 1-opioid receptor deficient CXBK mice, pretreatment with these selective delta-opioid receptor antagonists did not affect the morphine-induced place preference, although pretreatment with beta-funaltrexamine (beta-FNA: a selective mu-opioid receptor antagonist) significantly inhibited the morphine-induced place preference. [D-Pen2,D-Pen5]enkephalin (DPDPE: a delta 1-opioid receptor agonist) and [D-Ala2,Glu4]deltorphin (deltorphin II: a delta 2-opioid receptor agonist) induced a significant place preference in ddY mice, but not in CXBK mice. These results suggest that delta 1- and delta 2-opioid receptors in the nucleus accumbens that are related to the DPDPE- and deltorphin II-induced place preference may be dysfunctional and/or poor in CXBK mice. These findings also indicate that delta 1- and delta 2-opioid receptors may be involved in the modulation of the reinforcing effect of morphine.
研究了高选择性δ-阿片受体拮抗剂对ddY小鼠和μ1-阿片受体缺陷型CXBK小鼠吗啡诱导的位置偏爱效应。用纳曲吲哚（NTI：一种非选择性δ-阿片受体拮抗剂）、7-苄叉基纳曲酮（BNTX：一种选择性δ1-阿片受体拮抗剂）或纳曲苄（NTB：一种选择性δ2-阿片受体拮抗剂）预处理，可剂量依赖性地消除ddY小鼠吗啡诱导的位置偏爱。这些发现表明，吗啡诱导的位置偏爱可能由δ1-和δ2-阿片受体介导。另一方面，在μ1-阿片受体缺陷型CXBK小鼠中，用这些选择性δ-阿片受体拮抗剂预处理并不影响吗啡诱导的位置偏爱，尽管用β-氟纳曲胺（β-FNA：一种选择性μ-阿片受体拮抗剂）预处理可显著抑制吗啡诱导的位置偏爱。[D-青霉胺2，D-青霉胺5]脑啡肽（DPDPE：一种δ1-阿片受体激动剂）和[D-丙氨酸2，谷氨酸4]强啡肽（强啡肽II：一种δ2-阿片受体激动剂）在ddY小鼠中诱导出显著的位置偏爱，但在CXBK小鼠中未诱导出。这些结果表明，伏隔核中与DPDPE和强啡肽II诱导的位置偏爱相关的δ1-和δ2-阿片受体在CXBK小鼠中可能功能失调和/或功能不佳。这些发现还表明，δ1-和δ2-阿片受体可能参与吗啡强化作用的调节。
