AMPA receptor subunit GluR1 downstream of D-1 dopamine receptor stimulation in nucleus accumbens shell mediates increased drug reward magnitude in food-restricted rats.
AMPA receptor subunit GluR1 downstream of D-1 dopamine receptor stimulation in nucleus accumbens shell mediates increased drug reward magnitude in food-restricted rats.
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DOI：
10.1016/j.neuroscience.2009.11.015
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发表时间：
2010-02-17
期刊：
影响因子：
3.3
通讯作者：
Ziff, E. B.
中科院分区：
文献类型：
--
作者：
Carra, K. D.;Chau, L. S.;de Vaca, S. Cabeza;Gustafson, K.;Stouffer, M.;Tukey, D. S.;Restituito, S.;Ziff, E. B.
以往的研究结果表明，神经适应下游的D-1多巴胺（DA）受体的刺激，在丘脑核（NAc）参与增强药物奖励的慢性限食（FR）。鉴于NAc中D-1和GluR 1 AMPA受体的高共表达，以及GluR 1通道传导和D-1连接的细胞内信号级联的转运调节，本研究检测了D-1激动剂SKF-82958对NAc GluR 1磷酸化、颅内电自我刺激奖励（ICSS）和多胺GluR 1拮抗剂奖励效应的可逆性的影响，1-NA-精胺，在自由采食（AL）和FR大鼠中。全身给予SKF-82958或短暂摄入10%蔗糖溶液，可增加Ser 845上的NAc GluR 1磷酸化，但不增加Ser 831上的NAc GluR 1磷酸化，对FR大鼠的影响大于AL大鼠。在NAc壳中微量注射SKF-82958产生的奖励增强效应在FR大鼠中比在AL大鼠中更大，并且通过共注射1-NA-精胺来逆转。GluR 1丰度在整个细胞和突触体部分的NAc没有不同的喂养组之间，和微量注射AMPA，而影响ICSS，并没有发挥更大的影响FR比AL大鼠。这些结果表明，NAc GluR 1的奖励增强作用的D-1 DA受体刺激和增强FR的作用。此外，GluR 1参与似乎发生在下游的D-1 DA受体刺激，而不是反映基础增加GluR 1的表达或功能。基于Ser 845上GluR 1的磷酸化引发突触强化的证据，本研究结果可能反映了一种机制，通过该机制，FR通常促进奖励相关的学习，以在负能量平衡的压力下重新调整工具行为与环境突发事件。
Previous findings suggest that neuroadaptations downstream of D-1 dopamine (DA) receptor stimulation in nucleus accumbens (NAc) are involved in the enhancement of drug reward by chronic food restriction (FR). Given the high co-expression of D-1 and GluR1 AMPA receptors in NAc, and the regulation of GluR1 channel conductance and trafficking by D-1-linked intracellular signaling cascades, the present study examined effects of the D-1 agonist, SKF-82958, on NAc GluR1 phosphorylation, intracranial electrical self-stimulation reward (ICSS), and reversibility of reward effects by a polyamine GluR1 antagonist, 1-NA-spermine, in ad libitum fed (AL) and FR rats. Systemically administered SKF-82958, or brief ingestion of a 10% sucrose solution, increased NAc GluR1 phosphorylation on Ser845, but not Ser831, with a greater effect in FR than AL rats. Microinjection of SKF-82958 in NAc shell produced a reward-potentiating effect that was greater in FR than AL rats, and was reversed by co-injection of 1-NA-spermine. GluR1 abundance in whole cell and synaptosomal fractions of NAc did not differ between feeding groups, and microinjection of AMPA, while affecting ICSS, did not exert greater effects in FR than AL rats. These results suggest a role of NAc GluR1 in the reward-potentiating effect of D-1 DA receptor stimulation and its enhancement by FR. Moreover, GluR1 involvement appears to occur downstream of D-1 DA receptor stimulation rather than reflecting a basal increase in GluR1 expression or function. Based on evidence that phosphorylation of GluR1 on Ser845 primes synaptic strengthening, the present results may reflect a mechanism via which FR normally facilitates reward-related learning to re-align instrumental behavior with environmental contingencies under the pressure of negative energy balance.
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