The decreased cyclic-AMP dependent-protein kinase a function in the nucleus accumbens: A role in alcohol drinking but not in anxiety-like behaviors in rats
The decreased cyclic-AMP dependent-protein kinase a function in the nucleus accumbens: A role in alcohol drinking but not in anxiety-like behaviors in rats
复制标题
环-AMP 依赖性蛋白激酶 a 在大鼠脑核中的功能下降： 在大鼠饮酒而非焦虑样行为中发挥作用
DOI：
10.1038/sj.npp.1300900
复制
发表时间：
2006-07-01
影响因子：
7.6
通讯作者：
Pandey, Subhash C.
中科院分区：
文献类型：
--
作者：
Misra, Kaushik;Pandey, Subhash C.
伏隔核（NAc）脑结构与乙醇的奖励和强化特性有关。本研究探讨了伏隔核环AMP （cAMP）依赖性蛋白激酶A （PKA）信号在大鼠饮酒和焦虑样行为中的作用。通过升高+迷宫实验发现，将PKA抑制剂（Rp-cAMP）灌注到NAc壳中可以显著增加酒精的摄入量，但不能增加蔗糖的摄入量，而不会改变大鼠的焦虑样行为。PKA抑制剂注入NAc壳显著降低了PKA α -催化亚基（PKA- c α）和磷酸化cAMP反应元件结合蛋白（p-CREB）的蛋白水平，并降低了大鼠壳中神经肽Y （NPY）的蛋白水平，但NAc核中没有。另一方面，将PKA激活剂（Sp-cAMP）或NPY单独输注到NAc壳中，没有引起酒精摄入量的任何变化；然而，当这些药物与PKA抑制剂共同输注时，它们显著减弱了PKA药理抑制引起的酒精偏好的增加。有趣的是，PKA激活剂与PKA抑制剂共注入NAc壳后，PKA抑制剂诱导的大鼠NAc壳中PKA- c α和p-CREB以及NPY蛋白水平的降低显著正常化。综上所述，这些结果提供了第一个证据，证明NAc壳中PKA功能的下降与饮酒有关，但与大鼠的焦虑样行为无关。此外，PKA功能下降可能通过creb介导的NAc壳NPY表达下降来调节饮酒行为。
The nucleus accumbens (NAc) brain structures have been implicated in the reward and reinforcing properties of ethanol. The present study investigated the role of nucleus accumbal cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling in alcohol drinking and anxiety-like behaviors of rats. It was found that infusion of PKA inhibitor (Rp-cAMP) into the NAc shell significantly increased the alcohol but not the sucrose intake, without modulating the anxiety- like behaviors, as measured by elevated plus maze test in rats. PKA inhibitor infusion into the NAc shell significantly decreased the protein levels of alpha-catalytic subunit of PKA (PKA-C alpha) and phosphorylated cAMP response element-binding protein (p-CREB) as well as decreased the protein levels of neuropeptide Y (NPY) in the shell but not in the NAc core of rats. On the other hand, infusion of PKA activator (Sp-cAMP) or NPY alone into the NAc shell did not produce any changes in alcohol intake; however, when these agents were coinfused with PKA inhibitor, they significantly attenuated the increases in alcohol preference induced by pharmacological inhibition of PKA. Interestingly, PKA activator coinfusion with PKA inhibitor into the NAc shell significantly normalized the PKA inhibitor-induced decreases in the protein levels of PKA-C alpha and p-CREB as well as of NPY in the NAc shell of rats. Taken together, these results provide the first evidence that decreased PKA function in the NAc shell is involved in alcohol drinking but not in anxiety-like behaviors of rats. Furthermore, decreased function of PKA may regulate alcohol drinking behaviors via CREB-mediated decreased expression of NPY in the NAc shell of rats.