Suzuki T, Tsuji M, Mori T, Misawa M, Nagase H
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):293-9. doi: 10.1016/s0091-3057(96)00319-x.
The effects of the highly selective delta opioid receptor antagonists naltrindole (NTI) for delta 1 and delta 2 naltriben (NTB) and naltrindole 5'-isothiocyanate (5'-NTII) for delta 2 and 7-benzylidenenaltrexone (BNTX) for delta 1 on the development of physical dependence on morphine were investigated in mice. Neither NTI (3 mg/kg, sc), NTB (0.5 mg/kg, sc), 5'-NTII (0.5 mg/kg, sc) nor BNTX (0.5 mg/kg, sc) suppressed the antinociception induced by morphine (10 mg/kg, sc). Pretreatment with NTI (3 mg/kg, sc), NTB (0.5, 1.0 mg/kg, sc) or 5'-NTII (0.5, 1.0 mg/kg, sc) during chronic treatment with morphine for 5 days significantly suppressed naloxone-induced body-weight loss in morphine-dependent mice. The incidence of jumping and body shakes in morphine-dependent mice that were pretreated with NTI. NTB or 5'-NTII were significantly lower than with morphine alone. Pretreatment with BNTX (0.5, 1.0 mg/kg, sc) during chronic treatment with morphine also significantly suppressed naloxone-induced body-weight loss in morphine-dependent mice, but this suppression was weaker than that by the antagonists. In contrast to mice that had been pretreated with NTI, NTB or 5'-NTII, the incidence of several withdrawal signs, such a jumping and body shakes, was not significantly affected in morphine-dependent mice that were pretreated with BNTX. These findings suggest that both delta 2 and delta 1 opioid receptors may play important roles in modulating the development of physical dependence on morphine.
在小鼠中研究了高选择性δ阿片受体拮抗剂纳曲吲哚（NTI）（针对δ1）、纳曲苄（NTB）（针对δ1和δ2）、纳曲吲哚5'-异硫氰酸盐（5'-NTII）（针对δ2）和7-苄叉基纳曲酮（BNTX）（针对δ1）对吗啡身体依赖性形成的影响。NTI（3毫克/千克，皮下注射）、NTB（0.5毫克/千克，皮下注射）、5'-NTII（0.5毫克/千克，皮下注射）或BNTX（0.5毫克/千克，皮下注射）均未抑制吗啡（10毫克/千克，皮下注射）诱导的镇痛作用。在吗啡慢性治疗5天期间，用NTI（3毫克/千克，皮下注射）、NTB（0.5、1.0毫克/千克，皮下注射）或5'-NTII（0.5、1.0毫克/千克，皮下注射）预处理可显著抑制纳洛酮诱导的吗啡依赖小鼠体重减轻。用NTI、NTB或5'-NTII预处理的吗啡依赖小鼠的跳跃和身体颤抖发生率显著低于单独使用吗啡的小鼠。在吗啡慢性治疗期间，用BNTX（0.5、1.0毫克/千克，皮下注射）预处理也可显著抑制纳洛酮诱导的吗啡依赖小鼠体重减轻，但这种抑制作用比拮抗剂弱。与用NTI、NTB或5'-NTII预处理的小鼠不同，用BNTX预处理的吗啡依赖小鼠的几种戒断症状（如跳跃和身体颤抖）发生率未受到显著影响。这些发现表明，δ2和δ1阿片受体可能在调节吗啡身体依赖性的形成中都发挥重要作用。
