Department of Psychology, Purdue School of Science, Indiana University-Purdue University Indianapolis: 402 North Blackford Street, LD 124, Indianapolis, IN 46202, United States.
Pharmacol Biochem Behav. 2012 Mar;101(1):8-13. doi: 10.1016/j.pbb.2011.11.008. Epub 2011 Nov 18.
The central nucleus of the amygdala (CeA) has been implicated as having a significant role in mediating alcohol-drinking behavior. Neuropeptide Y (NPY) has been investigated as a potential pharmacotherapeutic due to its ability to attenuate ethanol intake, particularly when administered into the CeA. Previous research suggests, though the evidence is somewhat conflicting, that the efficacy of NPY is contingent upon genetic background and/or prior history of ethanol dependence in rats. However, studies looking at the effects of NPY in nonselected animals lacking a history of ethanol dependence have two factors that could impact the interpretation of the results: ethanol history/selection AND relatively low baseline ethanol intakes as compared to ethanol-dependent and/or genetically selected controls. The purpose of the present study was to generate higher baseline ethanol intakes upon which to examine the effects of NPY on ethanol and sucrose drinking in nonselected rats using a binge drinking model. Long Evans rats were trained to complete a single response requirement resulting in access to either 2% sucrose (Sucrose Group) or 2% sucrose/10% ethanol (Ethanol Group) for a 20-min drinking session. On treatment days, rats were bilaterally microinjected into the CeA with aCSF or one of three doses of NPY (0.25μg, 0.50μg, or 1.00μg/.5μL). Subjects in the Ethanol Group were consuming an average of 1.2g/kg of ethanol (yielding BELs of ~90mg%) during the 20min access period following aCSF treatments. The results revealed that NPY had no effect on either sucrose or ethanol consumption or on appetitive responding (latency to respond). Overall, the findings indicate that even a history of binge-like ethanol consumption is not sufficient to recruit CeA NPY activity, and are consistent with previous studies showing that the role of NPY in regulating ethanol reinforcement in the CeA may be contingent upon a prior history of ethanol dependence.
杏仁中央核(CeA)被认为在介导饮酒行为方面具有重要作用。神经肽 Y(NPY)因其能够减少乙醇摄入而被研究作为一种潜在的药物治疗方法,尤其是当它被注射到 CeA 中时。尽管证据有些矛盾,但之前的研究表明,NPY 的功效取决于大鼠的遗传背景和/或之前的乙醇依赖史。然而,研究 NPY 在缺乏乙醇依赖史的非选择性动物中的作用有两个因素可能会影响结果的解释:乙醇史/选择和与乙醇依赖和/或遗传选择对照相比,相对较低的基线乙醇摄入量。本研究的目的是在非选择性大鼠中产生更高的基线乙醇摄入量,然后使用 binge 饮酒模型研究 NPY 对乙醇和蔗糖摄入的影响。长耳大鼠接受训练,只需完成一次反应要求,即可在 20 分钟的饮酒时间内获得 2%蔗糖(蔗糖组)或 2%蔗糖/10%乙醇(乙醇组)。在治疗日,大鼠双侧脑室内注射 aCSF 或三种 NPY 剂量(0.25μg、0.5μg 或 1.0μg/.5μL)。在 aCSF 处理后,乙醇组的大鼠在 20 分钟的接触期内平均消耗 1.2g/kg 的乙醇(产生约 90mg%的 BEL)。结果表明,NPY 对蔗糖或乙醇的消耗或对食欲反应(反应潜伏期)没有影响。总体而言,这些发现表明,即使有 binge 样乙醇消耗史,也不足以招募 CeA NPY 活性,并且与之前的研究一致,表明 NPY 在调节 CeA 中乙醇强化的作用可能取决于之前的乙醇依赖史。