Tallett A J, Blundell J E, Rodgers R J
Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.
Behav Brain Res. 2008 Mar 5;187(2):417-27. doi: 10.1016/j.bbr.2007.10.005. Epub 2007 Oct 13.
Endogenous opioids have long been implicated in mechanisms of appetite control. A significant strand in the evidence base has been the hypophagic action of broad-spectrum opioid receptor antagonists (such as naloxone) in opiate-naïve animals. However, while much has been learned about sites of action, underlying receptor mechanisms and the role of taste hedonics, surprisingly little is known about the behavioural selectivity of naloxone-induced hypophagia. As such, two experiments employed detailed video analysis to profile the behavioural effects of naloxone (Experiment 1: 1.0-5.0 mg/kg; Experiment 2: 0.01-1.0 mg/kg) in non-deprived male rats during 1 h free-feeding tests with palatable mash. Results confirmed that, at doses > or =1.0 mg/kg, naloxone consistently suppresses food consumption and feeding behaviour but, congruent with its short biological half-life, had no carryover effects on post-treatment weight gain. Crucially, the anorectic doses of naloxone did not alter the time taken to find food or to commence feeding, the time spent feeding in the initial phase of testing, or the rate at which food was consumed. Furthermore, they neither interfered with non-ingestive components of the behavioural repertoire (e.g. locomotion, rearing) nor did they disrupt the normal structure of feeding behaviour (the behavioural satiety sequence, BSS). Rather, the principal effect of naloxone was to produce a shift to the left in (i.e. accelerate) the BSS. Findings are discussed in relation to the role of (mu) opioid receptor mechanisms in taste hedonics and the likelihood of a naloxone-induced reduction in the orosensory reward that would normally accompany/follow the ingestion of palatable food.
内源性阿片肽长期以来一直被认为与食欲控制机制有关。证据基础中的一个重要方面是,广谱阿片受体拮抗剂(如纳洛酮)在未接触过阿片类药物的动物中具有促食欲作用。然而,尽管我们已经对作用部位、潜在的受体机制以及味觉享乐主义的作用有了很多了解,但令人惊讶的是,对于纳洛酮诱导的食欲减退的行为选择性却知之甚少。因此,两项实验采用详细的视频分析来描述纳洛酮(实验1:1.0 - 5.0毫克/千克;实验2:0.01 - 1.0毫克/千克)在非饥饿雄性大鼠自由进食美味糊状食物1小时测试期间的行为效应。结果证实,剂量≥1.0毫克/千克时,纳洛酮持续抑制食物消耗和进食行为,但与其较短的生物半衰期一致,对治疗后体重增加没有残留影响。至关重要的是,纳洛酮的厌食剂量并未改变找到食物或开始进食所需的时间、测试初始阶段进食所花费的时间,或食物消耗的速率。此外,它们既不干扰行为库中的非摄食成分(如运动、站立),也不破坏进食行为的正常结构(行为饱足序列,BSS)。相反,纳洛酮的主要作用是使BSS向左移动(即加速)。我们将结合μ阿片受体机制在味觉享乐主义中的作用以及纳洛酮诱导的口腔感觉奖励减少的可能性来讨论这些发现,这种奖励通常会伴随/跟随美味食物的摄入。