Jethwa Preeti H, Barrett Perry, Turnbull Yvonne, Enright Rachel A, Warner Amy, Murphy Michelle, Ebling Francis J P
School of Biomedical Sciences and Institute of Neuroscience, University of Nottingham Medical School, Queen Medical Centre, Nottingham, UK.
Behav Pharmacol. 2009 Mar;20(2):155-65. doi: 10.1097/FBP.0b013e32832a8099.
Siberian hamsters develop hypophagia and increase catabolism of fat reserves in response to short photoperiods resulting in a natural loss of body weight in winter. We previously found that histamine 3 receptor (H3R) mRNA in the posterior hypothalamus is significantly decreased in short photoperiods. We hypothesized that this lower expression of H3R might contribute to the winter hypophagic state, therefore we examined the effects of the H3R agonist imetit and inverse agonists clobenpropit and thioperamide on food intake. We expressed the Siberian hamster H3R receptor in vitro and confirmed that imetit, clobenpropit and thioperamide are bound specifically, thus validating them as tools to investigate the role of H3R in vivo. Intracerebroventricular administration of histamine decreased food intake in hamsters in the fat summer state. Administration of imetit to hamsters in the lean state increased food intake, whereas administration of inverse agonists decreased food intake, though this was associated with decreased locomotor activity. Both H3R inverse agonists prevented the nocturnal rise in body temperature indicating additional effects on energy expenditure. In summary, our results suggest that increased availability of central histamine or the reduction of H3R activity decrease food intake. These effects are similar to those observed in hamsters in short photoperiods.
西伯利亚仓鼠在短光照周期下会出现摄食减少，并增加脂肪储备的分解代谢，导致冬季体重自然下降。我们之前发现，短光照周期下，下丘脑后部的组胺3受体（H3R）mRNA显著减少。我们推测，H3R的这种低表达可能导致冬季的低摄食状态，因此我们研究了H3R激动剂碘替丁以及反向激动剂氯苯丙胺和硫代哌啶对食物摄入的影响。我们在体外表达了西伯利亚仓鼠H3R受体，并证实碘替丁、氯苯丙胺和硫代哌啶能特异性结合，从而验证了它们作为研究H3R体内作用工具的有效性。向处于夏季肥胖状态的仓鼠脑室内注射组胺会减少其食物摄入量。向处于消瘦状态的仓鼠注射碘替丁会增加食物摄入量，而注射反向激动剂则会减少食物摄入量，不过这与运动活动减少有关。两种H3R反向激动剂都能阻止夜间体温升高，表明对能量消耗有额外影响。总之，我们的结果表明，中枢组胺可用性增加或H3R活性降低会减少食物摄入量。这些效应与在短光照周期下仓鼠中观察到的效应相似。
