Presynaptic inhibition of glutamate transmission by α2 receptors in the VTA.
Presynaptic inhibition of glutamate transmission by α2 receptors in the VTA.
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DOI：
10.1111/j.1460-9568.2012.08029.x
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Arencibia-Albite F
中科院分区：
文献类型：
--
作者：
Jiménez-Rivera CA;Figueroa J;Vázquez-Torres R;Vélez-Hernandez ME;Schwarz D;Velásquez-Martinez MC;Arencibia-Albite F
腹侧被盖区（VTA）是中皮质边缘系统的一部分，在药物滥用的奖赏和强化作用中起着关键作用。腹侧被盖区内的谷氨酸传输控制着目标导向行为和动机的重要方面。去甲肾上腺素能受体也存在于腹侧被盖区，在神经元活动的调节中具有重要功能。在这里，我们研究了α-2去甲肾上腺素能受体激活的雄性SD大鼠腹侧被盖区多巴胺能神经元谷氨酸神经传递的改变的影响。我们使用全细胞膜片钳记录从假定的腹侧被盖区多巴胺能神经元和测量兴奋性突触后电流。可乐定（40 μM）和UK 13，408（40 μM）（均为α-2受体激动剂）可降低谷氨酸诱导的兴奋性突触后电流的振幅（约40%）。可乐定给药后，在15-40 μM浓度范围内呈剂量依赖性降低。使用育亨宾（20μM）和另外两种α-2肾上腺素能受体拮抗剂idaxozan（40 μM）和阿替哌唑（20μM），我们证明了抑制作用是由α-2受体特异性介导的。此外，通过用H-7（75 μM）、RP-腺苷3′，5 ′-环（11 μM）和白屈菜红碱（1 μM）抑制蛋白激酶，表明可乐定诱导的抑制似乎涉及蛋白激酶C细胞内途径的选择性激活。增加的成对脉冲比和自发和微型兴奋性突触后电流频率的变化，但不振幅表明，α-2激动剂的作用是突触前介导的。提示谷氨酸对腹侧被盖区多巴胺能神经元兴奋性输入的抑制可能与奖赏和觅药行为的调节有关。
The ventral tegmental area (VTA) forms part of the mesocorticolimbic system and plays a pivotal role in reward and reinforcing actions of drugs of abuse. Glutamate transmission within the VTA controls important aspects of goal-directed behavior and motivation. Noradrenergic receptors also present in the VTA have important functions in the modulation of neuronal activity. Here we studied the effects of alpha-2 noradrenergic receptor activation in the alteration of glutamate neurotransmission in VTA dopaminergic neurons from male Sprague-Dawley rats. We used whole cell patch clamp recordings from putative VTA dopaminergic neurons and measured excitatory postsynaptic currents. Clonidine (40 μM) and UK 13,408 (40 μM), both alpha-2 receptor agonists, reduced (~ 40%) the amplitude of glutamate-induced excitatory postsynaptic currents. After clonidine administration, there was a dose-dependent reduction over the concentration range of 15–40 μM. Using yohimbine (20μM) and two other alpha-2 adrenergic receptor antagonists, idaxozan (40 μM) and atipemazole (20μM), we demonstrated that the inhibitory action is specifically mediated by alpha-2 receptors. Moreover, by inhibiting protein kinases with H-7 (75 μM), Rp-adenosine 3′,5′-cyclic (11 μM) and chelerythrine (1 μM) it was shown that the clonidine-induced inhibition seems to involve a selective activation of the protein kinase C intracellular pathway. An increased paired-pulse ratios and changes in spontaneous and miniature excitatory postsynaptic currents frequencies but not amplitudes indicated that the alpha-2 agonist’s effect was presynaptically mediated. It is suggested that the suppression of glutamate excitatory inputs onto VTA dopaminergic neurons might be relevant in the regulation of reward and drug seeking behaviors.
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影响因子：
7.6
作者：
Harris, GC;Aston-Jones, G
通讯作者：
Aston-Jones, G
影响因子：
5.5
作者：
Boehm, S
通讯作者：
Boehm, S
DOI：
10.1196/annals.1369.039
发表时间：
2006-01-01
期刊：
CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES
影响因子：
--
作者：
Jimenez-Rivera, Carlos A.;Feliu-Mojer, Monica;Vazquez-Torres, Rafael
通讯作者：
Vazquez-Torres, Rafael
影响因子：
3.3
作者：
GRACE, AA;BUNNEY, BS
通讯作者：
BUNNEY, BS
影响因子：
2.9
作者：
HIDAKA, H;INAGAKI, M;SASAKI, Y
通讯作者：
SASAKI, Y