The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking.

The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking.
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DOI:
10.1111/j.1369-1600.2010.00295.x
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发表时间:
2012-03
期刊:
影响因子:
3.4
通讯作者:
Bartlett SE
Bartlett SE
中科院分区:
医学2区
文献类型:
--
作者:
Nielsen CK;Simms JA;Bito-Onon JJ;Li R;Ananthan S;Bartlett SE

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治疗酒精使用障碍(AUD)的一个主要问题是由于压力和再次暴露于以前与酒精使用有关的线索或环境而导致的高复发率。应激源可能会导致人类再次饮酒或啮齿类动物恢复饮酒习惯。Delta阿片肽受体(DOP-Rs)在线索诱导的乙醇寻找恢复中起作用,但它们在应激诱导的乙醇寻找恢复中的作用尚不清楚。本研究的目的是确定DOP-Rs在育亨宾应激诱导的乙醇寻求恢复中的作用。雄性Long-Evans大鼠在每天30分钟的操作自我给药过程中使用FR3强化计划进行自我给药训练,然后进行消退训练。一旦达到消退标准,我们检测DOP-R拮抗剂Sori-9409(0-5 mg/kg,ip)对育亨宾(2 mg/kg,ip)应激诱导的恢复的影响。此外,还测定了DOP-R刺激的脑膜[35S]GTPγ与S的结合,并测定了血浆皮质酮(CORT)水平。Sori-9409可降低育亨宾应激诱导的乙醇恢复,但不影响育亨宾诱导的血浆皮质醇水平的升高。此外,育亨宾增加乙醇训练大鼠脑膜上DOP-R刺激的35[S]GTPγ与S的结合,该作用可被Sori-9409所抑制。这表明DOP-R在育亨宾应激诱导的乙醇寻找行为的恢复中起重要作用,DOP-R拮抗剂可能是治疗AUDS的有前途的候选药物。
A major problem in treating alcohol use disorders (AUDs) is the high rate of relapse due to stress and re-exposure to cues or an environment previously associated with alcohol use. Stressors can induce relapse to alcohol seeking in humans or reinstatement in rodents. Delta opioid peptide receptors (DOP-Rs) play a role in cue-induced reinstatement of ethanol-seeking, however their role in stress-induced reinstatement of ethanol-seeking is not known. The objective of this study was to determine the role of DOP-Rs in yohimbine-stress induced reinstatement of ethanol seeking. Male, Long-Evans rats were trained to self-administer 10% ethanol in daily 30 minute operant self administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP-R antagonist, SoRI-9409 (0-5 mg/kg, IP) on yohimbine (2 mg/kg, IP) stress-induced reinstatement. Additionally, DOP-R-stimulated [35S]GTPγS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pretreatment with SoRI-9409 decreased yohimbine stress-induced reinstatement of ethanol seeking but did not affect yohimbine-induced increases in plasma CORT levels. Additionally, yohimbine increased DOP-R-stimulated 35[S]GTPγS binding in brain membranes of ethanol-trained rats, an effect which was inhibited by SoRI-9409. This suggests that the DOP-R plays an important role in yohimbine stress-induced reinstatement of ethanol-seeking behavior and DOP-R antagonists may be promising candidates for further development as a treatment for AUDs.
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