Pharmacological stress is required for the anti-alcohol effect of the α3β4* nAChR partial agonist AT-1001.
Pharmacological stress is required for the anti-alcohol effect of the α3β4* nAChR partial agonist AT-1001.
复制标题
DOI：
10.1016/j.neuropharm.2015.02.005
复制
发表时间：
2015-06
影响因子：
4.7
通讯作者：
Toll L
中科院分区：
文献类型：
--
作者：
Cippitelli A;Brunori G;Gaiolini KA;Zaveri NT;Toll L
酒精和尼古丁经常一起服用。这种频繁的共同滥用背后的机制尚不清楚。遗传和药理学证据表明，含有α3和β4亚基的烟碱乙酰胆碱受体（nAChR）在酒精和尼古丁成瘾中起作用。AT-1001是一种高亲和力α3β4 nAChR部分激动剂，最近发现可阻断大鼠尼古丁自我给药和复发样行为。在此，为了研究α3β4 nAChR在调节酒精滥用的机制中的参与，我们评估了AT-1001对Sprague-Dawley大鼠酒精摄入和寻求的影响。在检查的最高剂量（3.0 mg/kg）下，AT-1001减少了操作性酒精自我给药，也观察到了食物自我给药的效果。1.5 mg/kg AT-1001（对酒精或食物自我给药无影响）基本消除了育亨宾（0.625 mg/kg）诱导的酒精寻求恢复，而酒精相关线索诱导的恢复未改变，AT-1001也未诱导自行消退的自我给药恢复。最后，AT-1001显示出抗焦虑活性时，测量在存在或不存在育亨宾应激的高架十字迷宫范例。总之，这些观察结果不支持α3β4 nAChR在介导酒精奖赏或线索诱导的酒精寻求复发中的特定参与，而是表明α3β4 nAChR部分激动可能构成治疗因应激反应升高而加重的酒精使用障碍的有吸引力的方法。
Alcohol and nicotine are often taken together. The mechanisms underlying this frequent co-abuse are not well known. Genetic and pharmacological evidence suggests that the nicotinic acetylcholine receptors (nAChRs) containing the α3 and β4 subunits play a role in alcohol as well as nicotine addiction. AT-1001 is a high affinity α3β4 nAChR partial agonist recently found to block nicotine self-administration and relapse-like behavior in rats. Here, to study the involvement of α3β4 nAChRs in the mechanisms that regulate alcohol abuse we evaluated the effects of AT-1001 on alcohol taking and seeking in Sprague-Dawley rats. AT-1001 reduced operant alcohol self-administration at the highest dose examined (3.0 mg/kg), an effect also observed for food self-administration. A dose of 1.5 mg/kg AT-1001, which had no effect on alcohol or food self-administration, essentially eliminated reinstatement of alcohol seeking induced by yohimbine (0.625 mg/kg) whereas, reinstatement induced by alcohol-associated cues was not altered, nor did AT-1001 induce reinstatement of extinguished self-administration on its own. Finally, AT-1001 showed an anxiolytic activity when measured in the presence or absence of yohimbine stress in the elevated plus maze paradigm. Together, these observations do not support a specific involvement of the α3β4 nAChR in mediating alcohol reward or cue-induced relapse to alcohol seeking but rather indicate that the α3β4 nAChR partial agonism may constitute an attractive approach for treating alcohol use disorders exacerbated by elevated stress response.
登录
查看更多内容
影响因子：
5
作者：
Glick, Stanley D.;Sell, Elizabeth M.;McCallum, Sarah E.;Maisonneuve, Isabelle M.
通讯作者：
Maisonneuve, Isabelle M.
DOI：
10.1523/jneurosci.2601-10.2010
发表时间：
2010-07-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hendrickson LM;Zhao-Shea R;Pang X;Gardner PD;Tapper AR
通讯作者：
Tapper AR
缰核：脊椎动物大脑中保守的不对称中继站。
DOI：
10.1098/rstb.2008.0213
发表时间：
2009-04-12
影响因子：
6.3
作者：
Bianco, Isaac H.;Wilson, Stephen W.
通讯作者：
Wilson, Stephen W.
影响因子：
1.7
作者：
Glick, SD;Maisonneuve, IM;Dickinson, HA
通讯作者：
Dickinson, HA
影响因子：
3.7
作者：
Caporaso N;Gu F;Chatterjee N;Sheng-Chih J;Yu K;Yeager M;Chen C;Jacobs K;Wheeler W;Landi MT;Ziegler RG;Hunter DJ;Chanock S;Hankinson S;Kraft P;Bergen AW
通讯作者：
Bergen AW