Activation of trace amine-associated receptor 1 attenuates nicotine withdrawal-related effects.
Activation of trace amine-associated receptor 1 attenuates nicotine withdrawal-related effects.
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DOI：
10.1111/adb.13075
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Li JX
中科院分区：
文献类型：
--
作者：
Wu R;Liu J;Johnson B;Huang Y;Zhang Y;Li JX
尼古丁成瘾是全球一种主要的可避免的脑部疾病。虽然尼古丁诱导了适度的强化效应，这对最初的药物使用很重要，但从尼古丁使用到尼古丁成瘾的转变涉及到导致药物戒断不良后果的机制。最近的研究表明，痕量胺相关受体1（TAAR 1）是一个很有前途的药理学靶点，用于调节尼古丁的正性增强作用。然而，TAAR1是否在尼古丁戒断的负强化中起作用仍有待确定。在这里，使用长距离（LA）自我给药模型，我们研究了与盐水和ShA大鼠相比，LA大鼠是否表现出尼古丁摄入量增加和戒断症状，然后测试了TAAR 1部分激动剂RO 5263397对尼古丁戒断作用的影响。我们发现，大鼠从长期访问组表现出显着的戒断诱导的焦虑样行为，机械超敏反应，数量增加的催促戒断症状和更高的药物的动机，而大鼠从短期访问没有不同的盐水组。TAAR 1部分激动剂RO 5263397显著降低了LA大鼠中尼古丁的身体和动机戒断作用，如高架十字迷宫（高架十字迷宫）试验中开放臂上花费的时间增加、爪退缩阈值正常化、戒断体征减少和自我给予尼古丁的动机所反映。这项研究表明，TAAR1的激活减弱了尼古丁戒断的负强化作用，并进一步表明TAAR1是治疗尼古丁成瘾的一个有前途的靶点。
Nicotine addiction is a leading avoidable brain disorder globally. Although nicotine induces a modest reinforcing effect, which is important for the initial drug use, the transition from nicotine use to nicotine addiction involves the mechanisms responsible for the negative consequences of drug abstinence. Recent study suggested that trace amine-associated receptor 1 (TAAR1) is a promising pharmacological target for the modulation of positive reinforcing effects of nicotine. However, whether TAAR1 plays a part in the negative reinforcement of nicotine withdrawal remains to be determined. Here, using a long-access (LA) self-administration model, we investigated whether LA rats show increased nicotine intake and withdrawal symptoms in comparison with saline and ShA rats and then tested the effect of TAAR1 partial agonist RO5263397 on nicotine withdrawal effects. We found that rats from long-access group showed significant abstinence-induced anxiety-like behaviour, mechanic hypersensitivity, increased number of precipitated withdrawal signs and higher motivation for the drug, while rats from short-access did not differ from saline group. TAAR1 partial agonist RO5263397 significantly reduced the physical and motivational withdrawal effects of nicotine in LA rats, as reflected by increased time spent on the open arm in the elevated plus maze (EPM) test, normalized paw withdrawal threshold, decreased withdrawal signs and motivation to self-administer nicotine. This study indicates that activation of TAAR1 attenuates the negative-reinforcing effects of nicotine withdrawal and further suggests TAAR1 as a promising target to treat nicotine addiction.
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DOI：
10.1523/jneurosci.2258-10.2010
发表时间：
2010-07-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bailey CD;De Biasi M;Fletcher PJ;Lambe EK
通讯作者：
Lambe EK
DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
11.1
作者：
George, Olivier;Ghozland, Sandy;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
4.6
作者：
Asif-Malik A;Hoener MC;Canales JJ
通讯作者：
Canales JJ
影响因子：
4.7
作者：
Jackson KJ;Muldoon PP;De Biasi M;Damaj MI
通讯作者：
Damaj MI
影响因子：
3.4
作者：
Cohen A;Treweek J;Edwards S;Leão RM;Schulteis G;Koob GF;George O
通讯作者：
George O