Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: interaction of GABA(B) and D2 receptors.
Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: interaction of GABA(B) and D2 receptors.
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DOI：
10.1016/j.neuroscience.2012.08.045
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发表时间：
2012-12-13
期刊：
影响因子：
3.3
通讯作者：
Brodie, M. S.
中科院分区：
文献类型：
--
作者：
Nimitvilai, S.;Arora, D. S.;Mcelvain, M. A.;Brodie, M. S.
腹侧被盖区（VTA）的神经元在药物滥用的奖励和强化特性中至关重要。腹侧被盖区神经元对中等浓度的多巴胺（DA）的脱敏依赖于蛋白激酶C（PKC）和细胞内钙水平。这种脱敏作用被称为DA抑制逆转（DA inhibition reversal，DA抑制逆转），因为它需要同时激活D2和D1样受体;单独激活D2受体不会导致脱敏作用。其他G蛋白连接受体的激活可以取代D1的激活。与D2受体一样，腹侧被盖区中的GABAB受体与G蛋白连接的钾通道偶联。在本研究中，我们研究了GABAB激动剂巴氯芬和多巴胺激动剂多巴胺和喹吡罗之间的相互作用，以确定GABAB和D2反应的脱敏过程中是否存在一些相互作用。长时间的巴氯芬单独给药产生逆转的巴氯芬诱导的抑制指示脱敏，这种脱敏持续至少60分钟后，巴氯芬洗脱。巴氯芬的脱敏作用依赖于蛋白激酶C。巴氯芬诱导脱敏后，多巴胺抑制作用降低了30分钟，相反，巴氯芬抑制作用的幅度降低了30分钟，长期应用多巴胺，但不喹吡罗。这些结果表明，D2和GABAB受体共享一些蛋白激酶C依赖的受体脱敏机制。
Neurons of the ventral tegmental area (VTA) are critical in the rewarding and reinforcing properties of drugs of abuse. Desensitization of VTA neurons to moderate extracellular concentrations of dopamine (DA) is dependent on protein kinase C (PKC) and intracellular calcium levels. This desensitization is called DA inhibition reversal (DIR), as it requires concurrent activation of D2 and D1-like receptors; activation of D2 receptors alone does not result in desensitization. Activation of other G-protein linked receptors can substitute for D1 activation. Like D2 receptors, GABAB receptors in the VTA are coupled to G-protein-linked potassium channels. In the present study, we examined interactions between a GABAB agonist, baclofen, and dopamine agonists, dopamine and quinpirole, to determine whether there was some interaction in the processes of desensitization of GABAB and D2 responses. Long-duration administration of baclofen alone produced reversal of the baclofen-induced inhibition indicative of desensitization, and this desensitization persisted for at least 60 min after baclofen washout. Desensitization to baclofen was dependent on protein kinase C. Dopamine inhibition was reduced for 30 min after baclofen-induced desensitization and conversely, the magnitude of baclofen inhibition was reduced for 30 min by long-duration application of dopamine, but not quinpirole. These results indicate that D2 and GABAB receptors share some protein kinase C-dependent mechanisms of receptor desensitization.
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影响因子：
5.3
作者：
Borgland, SL;Malenka, RC;Bonci, A
通讯作者：
Bonci, A
影响因子：
3.3
作者：
KALIVAS, PW;CHURCHILL, L;KLITENICK, MA
通讯作者：
KLITENICK, MA
DOI：
10.1523/jneurosci.0494-11.2011
发表时间：
2011-08-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
Wickman K
DOI：
10.1016/j.bbrc.2006.09.090
发表时间：
2006-11-24
影响因子：
3.1
作者：
Cho, Dong-Im;Beorn, SunRyeo;Kim, Kyeong-Man
通讯作者：
Kim, Kyeong-Man
影响因子：
2.9
作者：
Caille, I;Dumartin, B;Bloch, B
通讯作者：
Bloch, B