Nicotine activation of α4*receptors:: Sufficient for reward, tolerance, and sensitization
Nicotine activation of α4*receptors:: Sufficient for reward, tolerance, and sensitization
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DOI：
10.1126/science.1099420
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发表时间：
2004-11-05
期刊：
影响因子：
56.9
通讯作者：
Lester, HA
中科院分区：
文献类型：
--
作者：
Tapper, AR;McKinney, SL;Lester, HA
尼古丁受体亚型的身份足以引起尼古丁依赖的急性和慢性影响是未知的。我们用α 4烟碱亚基改造了突变小鼠，这些亚基在成孔M2结构域中含有一个点突变Leu（9）' --> Ala（9）'，使α 4 * 受体对尼古丁过敏。低剂量激动剂对α 4 * 烟碱乙酰胆碱受体的选择性激活重现了被认为在依赖性中重要的尼古丁效应，包括对急性尼古丁给药的反应强化，以及慢性尼古丁给药引起的耐受性和致敏性。这些数据表明，α 4 * 受体的激活足以产生尼古丁诱导的奖赏、耐受和敏化。
The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with alpha4 nicotinic subunits containing a single point mutation, Leu(9)' --> Ala(9)' in the pore-forming M2 domain, rendering alpha4* receptors hypersensitive to nicotine. Selective activation of alpha4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of alpha4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization.