Metabotropic glutamate 2/3 receptors in the ventral tegmental area and the nucleus accumbens shell are involved in behaviors relating to nicotine dependence
Metabotropic glutamate 2/3 receptors in the ventral tegmental area and the nucleus accumbens shell are involved in behaviors relating to nicotine dependence
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DOI：
10.1523/jneurosci.1766-07.2007
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发表时间：
2007-08-22
影响因子：
5.3
通讯作者：
Markou, Athina
中科院分区：
文献类型：
--
作者：
Liechti, Matthias E.;Lhuillier, Loic;Markou, Athina
维持尼古丁自我给药和依赖性的动机可能涉及多巴胺能神经传递的改变。代谢型谷氨酸（mGlu）2/3受体调节腹侧被盖区（VTA）和背核（NAc）壳中谷氨酸和多巴胺的释放，这两个脑区与奖励和动机过程密切相关。我们发现，急性全身以及VTA内或NAc内给予mGlu 2/3受体激动剂LY 379268 [（-）-2-氧杂-4-氨基双环[3.1.0]己烷-4，6-二羧酸酯]可减少大鼠的尼古丁自我给药，但不减少食物给药。此外，尼古丁自身给药下调了皮质边缘大鼠脑部位（包括VTA和NAc）的mGlu 2/3受体功能，这通过[S-35] GTP γ S结合试验中mGlu 2/3受体与G蛋白的偶联减少得到证明。此外，在14天治疗期开始时，LY 379268重复治疗减少了尼古丁自我给药;然而，获得的尼古丁输注次数逐渐恢复至基线水平，表明对LY 379268重复治疗效应的耐受性。最后，LY 379268给药降低了尼古丁和食物寻求行为的线索诱导的恢复。总之，这些研究结果表明，在后腹侧被盖区和NAc壳的mGlu 2/3受体的重要作用，在尼古丁的奖励作用的调解和潜在的线索诱导的尼古丁寻求行为。
The motivation to maintain nicotine self-administration and dependence may involve alterations in glutamatergic neurotransmission. Metabotropic glutamate ( mGlu) 2/3 receptors regulate glutamate and dopamine release in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) shell, two brain areas critically involved in reward and motivational processes. We found that acute systemic, as well as intra-VTA or intra-NAc, administration of the mGlu2/3 receptor agonist LY379268 [(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate] decreased nicotine, but not food, self-administration in rats. In addition, nicotine self-administration downregulated mGlu2/3 receptor function in corticolimbic rat brain sites including the VTA and the NAc, demonstrated by decreased coupling of mGlu2/3 receptors to G-proteins in the [S-35] GTP gamma S binding assay. Furthermore, repeated treatment with LY379268 reduced nicotine self-administration at the beginning of a 14 d treatment period; however, the number of nicotine infusions earned gradually returned to baseline levels, indicating tolerance to the effects of repeated LY379268 treatment. Finally, LY379268 administration decreased both cue-induced reinstatement of nicotine-and food-seeking behavior. Together, these findings indicate an important role for mGlu2/3 receptors in the posterior VTA and the NAc shell in the mediation of the rewarding effects of nicotine and potentially in cue-induced nicotine-seeking behavior.