Heinrichs S C, Lapsansky J, Lovenberg T W, De Souza E B, Chalmers D T
Neurocrine Biosciences, Inc., San Diego, CA 92121, USA.
Regul Pept. 1997 Jul 23;71(1):15-21. doi: 10.1016/s0167-0115(97)01005-7.
The recent identification and differential localization in brain of three binding sites for corticotropin-releasing factor (CRF)-like peptides (CRF1 and CRF2 receptors as well as CRF-binding protein) suggest the existence of functionally distinct neurobiological systems which mediate CRF activation. For instance, evidence from receptor knockdown and pharmacological studies suggest involvement of the CRF1 receptor in anxiogenic-like behavior and the CRF-binding protein in learning and memory processes. The present studies examined the potential functional significance of the CRF2 receptor in relation to the CRF1 receptor using two animal models of anxiety and endocrine reactivity to a stressor. CRF1 and CRF2 receptor knockdown was achieved and confirmed autoradiographically within brain regions relevant to behavioral reactivity to stressors by chronic, central administration of antisense oligonucleotides. CRF1 but not CRF2, know down produced a significant anxiolytic-like effect in the Defensive Withdrawal relative to vehicle-treated and two missense oligonucleotide negative control groups. In contrast, neither antisense treatment altered endocrine or behavioral reactivity to a swim stressor. Thus, the present data support the reported role of CRF1 receptors in the mediation of anxiogenic-like behavior and suggest a functionally distinct for role for CRF2 receptors in brain.
最近在大脑中对促肾上腺皮质激素释放因子（CRF）样肽的三个结合位点（CRF1和CRF2受体以及CRF结合蛋白）进行的鉴定和差异定位表明，存在功能不同的神经生物学系统来介导CRF激活。例如，来自受体敲低和药理学研究的证据表明，CRF1受体参与了焦虑样行为，而CRF结合蛋白参与了学习和记忆过程。本研究使用两种焦虑动物模型和对应激源的内分泌反应，研究了CRF2受体相对于CRF1受体的潜在功能意义。通过慢性、中枢给予反义寡核苷酸，在与应激源行为反应相关的脑区实现并通过放射自显影证实了CRF1和CRF2受体的敲低。相对于载体处理组和两个错义寡核苷酸阴性对照组，CRF1而非CRF2的敲低在防御性退缩中产生了显著的抗焦虑样效应。相反，两种反义处理均未改变对游泳应激源的内分泌或行为反应。因此，本数据支持了CRF1受体在介导焦虑样行为中的报道作用，并表明CRF2受体在大脑中具有功能上不同的作用。
