Specificity of Varenicline in Blocking Mesolimbic Circuit Activation to Natural and Drug Rewards.
Specificity of Varenicline in Blocking Mesolimbic Circuit Activation to Natural and Drug Rewards.
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DOI：
10.1016/j.neuroscience.2021.12.016
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发表时间：
2022-02-10
期刊：
影响因子：
3.3
通讯作者：
Betley JN
中科院分区：
文献类型：
--
作者：
Goldstein N;Carty JRE;Betley JN
The mesolimbic dopamine (DA) system reinforces behaviors that are critical for survival. However, drug dependence can occur when drugs of abuse, such as nicotine, highjack this reinforcement system. Pharmacologically targeting the DA system to selectively block drug reinforcement requires a detailed understanding of the neural circuits and molecular pathways that lead to the reward-based activation of mesolimbic circuits. Varenicline is an approved smoking cessation drug that has been shown to block nicotine-evoked DA increases in the nucleus accumbens (NAc) through action on nicotinic acetylcholine receptors. Because these receptors have been implicated in the reinforcement of other addictive substances, we explored the possibility that varenicline could broadly affect reward processing. We used in vivo fiber photometry to monitor midbrain DA neuron activity and striatal DA levels following either natural or drug rewards in mice treated with varenicline. We demonstrate that varenicline pretreatment enhances the suppression of nicotine-evoked DA release by attenuating DA neuron activity in the VTA. Varenicline’s ability to attenuate DA release is highly specific to nicotine, and varenicline slightly elevates DA release when co-administered with morphine or ethanol. Furthermore, varenicline has no effect on DA release in response to naturally rewarding behavior such as food intake or exercise. These results demonstrate the exquisite specificity with which varenicline blocks nicotine reward and highlight the complexity with which different rewards activate the mesolimbic DA system.
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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
影响因子：
4.7
作者：
Lammel S;Lim BK;Malenka RC
通讯作者：
Malenka RC
影响因子：
4.8
作者：
Lee AM;Mansuri MS;Wilson RS;Lam TT;Nairn AC;Picciotto MR
通讯作者：
Picciotto MR
影响因子：
7.6
作者：
Di Ciano, Patricia;Guranda, Mihail;Le Foll, Bernard
通讯作者：
Le Foll, Bernard
影响因子：
7.3
作者：
Feduccia, A. A.;Simms, J. A.;Bartlett, S. E.
通讯作者：
Bartlett, S. E.