Department of Experimental Psychology, Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK.
Br J Pharmacol. 2012 Jul;166(6):1815-21. doi: 10.1111/j.1476-5381.2012.01888.x.
BACKGROUND AND PURPOSE Endocannabinoid systems are strongly implicated in the physiological control of appetite and eating behaviour, with cannabinoid CB(1) receptor agonists and antagonists, respectively, increasing or decreasing food intake. This study examined the acute actions of the putative endocannabinoid noladin ether on food intake and eating motivation, assessing how it affects the amount of work expended by animals to obtain food. EXPERIMENTAL APPROACH Non-deprived male rats were injected systemically with noladin ether to assess its acute effects on ad libitum feeding of a standard laboratory diet. Additionally, the effects of noladin on lever pressing for palatable food were determined using a progressive ratio (PR) operant paradigm. KEY RESULTS Noladin dose dependently increased 2 h food intake, with a significant effect over 1 h after a dose of 0.5 mg·kg(-1). In the PR test, this hyperphagic dose of noladin ether promoted sustained high rates of responding and significantly increased the total number of lever presses and break-point. These latter effects were prevented by pretreatment with 1.0 mg·kg(-1) of the selective CB(1) antagonist surinabant (SR147778), that alone had no effect on responding. CONCLUSIONS AND IMPLICATIONS This is the first report of hyperphagia induced by acute noladin administration, and the first description of behavioural actions in rats. Consistent with prevailing notions about the role of endocannabinoids in appetite, a hyperphagic dose of noladin markedly increased efforts expended by animals to obtain food. Thus, noladin exerts a specific action on eating motivation; possibly promoting eating by increasing the incentive value of food.
内源性大麻素系统强烈参与了食欲和进食行为的生理控制，大麻素 CB1 受体激动剂和拮抗剂分别增加或减少食物摄入。本研究检查了拟议的内源性大麻素诺拉醚对食物摄入和进食动机的急性作用，评估了它如何影响动物获得食物所付出的努力量。
非剥夺雄性大鼠系统注射诺拉醚，以评估其对标准实验室饮食的自由进食的急性影响。此外，使用递增比率（PR）操作范式确定诺拉对美味食物按压的影响。
诺拉剂量依赖性地增加了 2 小时的食物摄入量，在剂量为 0.5mg·kg-1 后 1 小时内有显著效果。在 PR 测试中，这种高剂量的诺拉醚促进了持续的高反应率，并显著增加了总按压次数和断点。这些后期效果被 1.0mg·kg-1 的选择性 CB1 拮抗剂 surinabant（SR147778）预处理所预防，而单独使用 surinabant 对反应没有影响。
这是首次报道急性诺拉给药引起的暴食，也是首次描述大鼠的行为作用。与内源性大麻素在食欲中的作用的普遍观念一致，诺拉的高剂量显著增加了动物为获得食物而付出的努力。因此，诺拉对进食动机有特定的作用；可能通过增加食物的激励价值来促进进食。
