Obesity is a prevalent disease, but effective treatment options remain limited. Agonists of the alpha-7 nicotinic acetylcholine receptor (α7nAChR) promote negative energy balance in mice, but these effects are not well-studied in rats. We tested the hypothesis that central administration of the α7nAChR agonist PHA-543613 (PHA) would decrease food intake and body weight in adult male Sprague Dawley rats. Intracerebroventricular (ICV) PHA administration in chow-fed rats produced a suppression of energy intake and weight gain over 24 h. Next, to evaluate effects of ICV PHA on palatable food intake, rats were maintained on a choice diet of rodent chow and 45 % high fat diet (HFD); under these conditions, ICV PHA produced no significant changes in energy intake from either food, or body weight gain, in the 24 h post-injection. However, when given a choice of chow or a higher-fat 60 % HFD, ICV PHA reduced intake of 60 % HFD, but not chow; body weight gain was also suppressed. Further experiments evaluating conditioned taste avoidance (CTA) and pica in response to ICV PHA suggested that the suppressive food intake and body weight effects after ICV injection of PHA were not due to nausea/malaise. Finally, an operant conditioning study showed that responding on a progressive ratio schedule of reinforcement for high-fat food pellets decreased after ICV PHA. Collectively, these studies show that PHA reduces energy intake under some but not all dietary conditions. Importantly, central PHA decreases both food intake as well as motivation for highly palatable, energy dense foods in rats without inducing nausea/malaise, suggesting that the α7nAChR could be a viable target for developing treatments for obesity.

中文翻译：

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α-7 烟碱乙酰胆碱受体激动剂 PHA-543613 可减少雄性大鼠的食物摄入量

肥胖是一种普遍性疾病，但有效的治疗选择仍然有限。α7 烟碱乙酰胆碱受体 (α7nAChR) 激动剂可促进小鼠的能量负平衡，但这些作用在大鼠中尚未得到充分研究。我们测试了以下假设：α7nAChR 激动剂 PHA-543613 (PHA) 的中央给药会减少成年雄性 Sprague Dawley 大鼠的食物摄入量和体重。脑室内 (ICV) PHA 给予饲料喂养的大鼠，在 24 小时内抑制能量摄入和体重增加。接下来，为了评估 ICV PHA 对适口食物摄入的影响，大鼠维持精选的啮齿动物饲料和 45% 高脂肪饮食 (HFD)；在这些条件下，ICV PHA 在注射后 24 小时内对食物能量摄入或体重增加没有产生显着变化。然而，当选择食物或高脂肪 60% HFD 时，ICV PHA 减少了 60% HFD 的摄入量，但不减少食物；体重增加也受到抑制。进一步的实验评估了条件性味觉回避 (CTA) 和异食癖对 ICV PHA 的反应，表明 ICV 注射 PHA 后抑制食物摄入和体重的影响并不是由于恶心/不适。最后，一项操作性条件反射研究表明，在 ICV PHA 后，对高脂肪食物颗粒的渐进比例强化计划的反应有所下降。总的来说，这些研究表明，PHA 在某些但并非所有饮食条件下都会减少能量摄入。重要的是，中枢 PHA 会降低大鼠的食物摄入量以及对高适口性、能量密集型食物的动机，而不会引起恶心/不适，这表明 α7nAChR 可能是开发肥胖治疗方法的可行靶点。