Use of home cage wheel running to assess the behavioural effects of administering a mu/delta opioid receptor heterodimer antagonist for spontaneous morphine withdrawal in the rat.
Use of home cage wheel running to assess the behavioural effects of administering a mu/delta opioid receptor heterodimer antagonist for spontaneous morphine withdrawal in the rat.
复制标题
使用式家用笼子跑步来评估施用MU/Delta阿片受体异二聚体拮抗剂的行为效应，以便大鼠自发性吗啡戒断。
DOI：
10.1016/j.bbr.2020.112953
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发表时间：
2021-01-15
影响因子：
2.7
通讯作者：
Streicher JM
中科院分区：
文献类型：
--
作者：
Morgan MM;Peecher DL;Streicher JM
阿片类药物滥用是一个重大的健康问题。本研究的目的是评估雄性大鼠mu-/delta-阿片受体（MOR/DOR）异源二聚体的新型拮抗剂（D24M）的潜在破坏性副作用和治疗潜力。将高剂量的D24M（1和10 nmol）注入侧脑室不影响家鼠笼轮的运转。每日2次递增剂量吗啡（5 ~ 20 mg/kg），持续5天，可抑制小鼠轮式跑动，并通过热板试验诱导抗伤感受性耐受。给药D24M对吗啡耐受无影响，但有延长非耐受大鼠吗啡抗痛觉的倾向。自发的吗啡戒断明显表现为体重下降，在昼夜节律周期正常活跃的黑暗阶段，车轮跑的减少和睡眠的增加，在正常不活跃的光明阶段，车轮跑的增加和清醒。停药第3天暗期给药D24M对车轮运转无影响。这些数据为家庭笼轮跑步作为评估大鼠自发性阿片类药物戒断的方法的临床相关性提供了额外的证据。这些数据还表明，阻断MOR/DOR异源二聚体不会产生破坏性副作用或阻断吗啡的抗感觉作用。虽然给药D24M对吗啡戒断无影响，但需要进一步的研究来评估持续给药吗啡和其他阿片类药物对持续疼痛大鼠的戒断。
Opioid abuse is a major health problem. The objective of the present study was to evaluate the potentially disruptive side effects and therapeutic potential of a novel antagonist (D24M) of the mu-/delta-opioid receptor (MOR/DOR) heterodimer in male rats. Administration of high doses of D24M (1 & 10 nmol) into the lateral ventricle did not disrupt home cage wheel running. Repeated twice daily administration of increasing doses of morphine (5 to 20 mg/kg) over 5 days depressed wheel running and induced antinociceptive tolerance measured with the hot plate test. Administration of D24M had no effect on morphine tolerance, but tended to prolong morphine antinociception in non-tolerant rats. Spontaneous morphine withdrawal was evident as a decrease in body weight, a reduction in wheel running and an increase in sleep during the normally active dark phase of the circadian cycle, and an increase in wheel running and wakefulness in the normally inactive light phase. Administration of D24M during the dark phase on the third day of withdrawal had no effect on wheel running. These data provide additional evidence for the clinical relevance of home cage wheel running as a method to assess spontaneous opioid withdrawal in rats. These data also demonstrate that blocking the MOR/DOR heterodimer does not produce disruptive side effects or block the antinociceptive effects of morphine. Although administration of D24M had no effect on morphine withdrawal, additional studies are needed to evaluate withdrawal to continuous morphine administration and other opioids in rats with persistent pain.
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炎症引起的大鼠炎症引起的家用笼子抑制的分析揭示了阿片类药物抗伤害感和功能恢复之间的差异。
影响因子：
2.7
作者：
Kandasamy, Ram;Calsbeek, Jonas J.;Morgan, Michael M.
通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
7.3
作者：
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通讯作者：
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影响因子：
3.6
作者：
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通讯作者：
Morgan, Michael M.
影响因子：
2.5
作者：
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通讯作者：
Perrotti, Linda I.