Department of Psychology, Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA.
Addict Biol. 2012 Mar;17(2):338-50. doi: 10.1111/j.1369-1600.2011.00336.x. Epub 2011 Jul 18.
Neuropeptide Y (NPY) and protein kinase A (PKA) have been implicated in neurobiological responses to ethanol. We have previously reported that mutant mice lacking normal production of the RIIβ subunit of PKA (RIIβ-/- mice) show enhanced sensitivity to the locomotor stimulant effects of ethanol and increased behavioral sensitization relative to littermate wild-type RIIβ+/+ mice. We now report that RIIβ-/- mice also show increased NPY immunoreactivity in the nucleus accumbens (NAc) core and the ventral striatum relative to RIIβ+/+ mice. These observations suggest that elevated NPY signaling in the NAc and/or striatum may contribute to the increased sensitivity to ethanol-induced behavioral sensitization that is a characteristic of RIIβ-/- mice. Consistently, NPY-/- mice failed to display ethanol-induced behavioral sensitization that was evident in littermate NPY+/+ mice. To examine more directly the role of NPY in the locomotor stimulant effects of ethanol, we infused a recombinant adeno-associated virus (rAAV) into the region of the NAc core of DBA/2J mice. The rAAV-fibronectin (FIB)-NPY(13-36) vector expresses and constitutively secretes the NPY fragment NPY(13-36) (a selective Y(2) receptor agonist) from infected cells in vivo. Mice treated with the rAAV-FIB-NPY(13-36) vector exhibited reduced expression of ethanol-induced behavioral sensitization compared with mice treated with a control vector. Taken together, the current data provide the first evidence that NPY signaling in the NAc core and the Y(2) receptor modulate ethanol-induced behavioral sensitization.
神经肽 Y（NPY）和蛋白激酶 A（PKA）已被牵涉到对乙醇的神经生物学反应中。我们之前曾报道过，缺乏 PKA 的正常 RIIβ 亚基产生的突变小鼠（RIIβ-/- 小鼠）相对于同窝野生型 RIIβ+/+ 小鼠，表现出对乙醇的运动兴奋剂作用的敏感性增强和行为敏化增加。我们现在报告说，与 RIIβ+/+ 小鼠相比，RIIβ-/- 小鼠的伏隔核（NAc）核心和腹侧纹状体中的 NPY 免疫反应性也增加。这些观察结果表明，NAc 和/或纹状体中升高的 NPY 信号可能有助于增加 RIIβ-/- 小鼠对乙醇诱导的行为敏化的敏感性。一致地，NPY-/- 小鼠未能表现出在同窝 NPY+/+ 小鼠中明显的乙醇诱导的行为敏化。为了更直接地研究 NPY 在乙醇的运动兴奋剂作用中的作用，我们将重组腺相关病毒（rAAV）注入 DBA/2J 小鼠的 NAc 核心区域。rAAV-纤维连接蛋白（FIB）-NPY（13-36）载体在体内从受感染的细胞中表达并持续分泌 NPY 片段 NPY（13-36）（一种选择性 Y2 受体激动剂）。用 rAAV-FIB-NPY（13-36）载体处理的小鼠与用对照载体处理的小鼠相比，表现出乙醇诱导的行为敏化表达减少。总之，当前的数据提供了第一个证据，表明 NAc 核心中的 NPY 信号和 Y2 受体调节乙醇诱导的行为敏化。
