Kappa-opioid receptors and relapse-like drinking in long-term ethanol-experienced rats
Kappa-opioid receptors and relapse-like drinking in long-term ethanol-experienced rats
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DOI：
10.1007/s002130000601
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发表时间：
2000-12-01
影响因子：
3.4
通讯作者：
Spanagel, R
中科院分区：
文献类型：
--
作者：
Hölter, SM;Henniger, MSH;Spanagel, R
理由：强啡肽/κ-阿片受体系统在乙醇强化中的作用尚不清楚。目的：检查高选择性 kappa -阿片受体激动剂 CI-977（依那多林）和长效选择性 kappa -阿片受体拮抗剂去甲二托菲明 (nor-BNI) 对长期饮酒大鼠的戒酒效应 (ADE) 测量的复发样饮酒的影响。方法：给大鼠植入微型渗透泵，每小时输送 0 或 0.01 mg/kg CI-977，或者在四瓶笼式饮酒模式中禁酒 2 周后，在表现酒精之前接受两次（间隔 12 小时）nor-BNI（0 或 5 mg/kg 腹腔注射）注射。在第二个实验中，长期接触乙醇的大鼠在操作性乙醇自我给药模式中接受急性 CI-977 治疗（0、0.003-0.1 mg/kg 腹腔注射）或在 23 小时疗程前注射两次（间隔 12 小时）nor-BNI（0 或 5 mg/kg 腹腔注射）。结果：慢性 CI-977 增强了 ADE 期间的乙醇摄入量和偏好。急性 CI-977 剂量依赖性地降低总杠杆按压活动，表现出非特异性镇静作用，但最低剂量 (0.003 mg/kg) 除外，该剂量选择性增加基础饮酒期间对乙醇的杠杆按压。 Nor-BNI 根本不会影响复发性饮酒。结论：刺激κ-阿片受体可以增加乙醇摄入量，至少在长期接触乙醇的大鼠中是这样。由于κ-阿片受体激动剂具有令人厌恶的动机后果，因此增加饮酒可能是抵消这种治疗的厌恶作用的一种尝试。另一方面，nor-BNI 实验表明，内源性 kappa -阿片受体刺激似乎与长期戒酒后的复发样饮酒无关。
Rationale: The role of the dynorphin/kappa -opioid receptor system in ethanol reinforcement is unclear. Objective: Examination of the effects of the highly selective kappa -opioid receptor agonist CI-977 (enadoline) and of the long-acting selective kappa -opioid receptor antagonist nor-binaltorphimine (nor-BNI) on relapse-like drinking measured by the alcohol deprivation effect (ADE) in long-term ethanol-experienced rats. Methods: Rats were either implanted with mini-osmotic pumps delivering 0 or 0.01 mg/kg per h CI-977 or received two injections (12 h apart) of nor-BNI (0 or 5 mg/kg i.p.) before representation of alcohol after 2 weeks of alcohol deprivation in a four-bottle home cage drinking paradigm. In a second experiment, long-term ethanol-experienced rats trained in an operant ethanol self-administration paradigm received either acute CI-977 treatment (0, 0.003-0.1 mg/kg i.p.) or two injections (12 h apart) of nor-BNI (0 or 5 mg/kg i.p.) before a 23-h session. Results: Chronic CI-977 potentiated ethanol intake and preference during the ADE. Acute CI-977 dose-dependently reduced total lever pressing activity demonstrating an unspecific sedative effect, except for the lowest dose (0.003 mg/kg), which selectively increased lever pressing for ethanol during basal drinking. Nor-BNI did not affect relapse-like drinking at all. Conclusions: Stimulation of kappa -opioid receptors can increase ethanol intake, at least in long-term ethanol-experienced rats. Since kappa -opioid receptor agonists have aversive motivational consequences, increased ethanol drinking might be an attempt to counteract the aversive effects of this treatment. On the other hand, the nor-BNI experiments indicate that endogenous kappa -opioid receptor stimulation does not seem to be involved in relapse-like drinking after protracted abstinence.