Jones D N, Kortekaas R, Slade P D, Middlemiss D N, Hagan J J
Neuroscience Research, SmithKline Beecham Pharmaceuticals plc, Harlow, Essex, UK.
Psychopharmacology (Berl). 1998 Jul;138(2):124-32. doi: 10.1007/s002130050654.
The present study determined the behavioural effects of the corticotropin releasing factor (CRF)-related peptides, human/rat CRF (h/rCRF), ovine CRF (oCRF), sauvagine (SAUV), urotensin I (UT) and the recently discovered neuropeptide, rat urocortin (rUCN). All of the peptides dose-dependently increased motor activity in a familiar environment and reduced feeding in hungry rats. There was no apparent relationship between potency/affinity at CRF2 receptors and effects in these two tests. In a comparison of h/rCRF and rUCN upon discrete spontaneous behaviours, both peptides (3.0 microg i.c.v.) increased activity and grooming, induced a fore-paw tremor and reduced the incidence of motionlessness. However, h/rCRF reduced motionlessness to a greater extent and was a more potent inducer of defaecation, weight loss, oral movements and fore-paw tremor than rUCN. In the elevated X maze, both h/rCRF and rUCN (1.0 microg i.c.v.) had anxiogenic-like effects upon behaviour. In contrast, h/rCRF (1.0 microg i.c.v.), but not rUCN (1.0-10 microg i.c.v.) increased the startle response to an acoustic stimulus. In summary, all the CRF-related peptides increased motor activity and reduced feeding in rats in a similar manner and both rUCN and h/rCRF induced anxiogenesis. However, there were some behavioural differences between rUCN and h/rCRF which require further study. Further pharmacological investigation of the role of CRF receptor subtypes requires the use of subtype selective antagonists.
本研究确定了促肾上腺皮质激素释放因子(CRF)相关肽类,即人/大鼠CRF(h/rCRF)、羊CRF(oCRF)、蛙皮素(SAUV)、尾加压素I(UT)以及最近发现的神经肽——大鼠尿皮质素(rUCN)的行为效应。所有这些肽类均呈剂量依赖性地增加熟悉环境中大鼠的运动活性,并减少饥饿大鼠的进食量。在这两项试验中,CRF2受体的效价/亲和力与效应之间没有明显关系。在比较h/rCRF和rUCN对离散自发行为的影响时,两种肽(脑室内注射3.0微克)均增加了活动和梳理行为,诱发前爪震颤,并降低了静止不动的发生率。然而,h/rCRF比rUCN更能有效地减少静止不动的时间,并且在诱导排便、体重减轻、口腔运动和前爪震颤方面更具效力。在高架十字迷宫中,h/rCRF和rUCN(脑室内注射1.0微克)对行为均有类似焦虑的影响。相比之下,h/rCRF(脑室内注射1.0微克)可增加对听觉刺激的惊吓反应,而rUCN(脑室内注射1.0 - 10微克)则无此作用。总之,所有CRF相关肽类均以相似方式增加大鼠的运动活性并减少进食量,rUCN和h/rCRF均可诱发焦虑。然而,rUCN和h/rCRF之间存在一些行为差异,需要进一步研究。对CRF受体亚型作用的进一步药理学研究需要使用亚型选择性拮抗剂。