Zieba Barbara, Grzegorzewska Małgorzata, Brański Piotr, Domin Helena, Wierońska Joanna M, Hess Grzegorz, Smiałowska Maria
Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 Cracow, Poland.
Neuropeptides. 2008 Oct-Dec;42(5-6):513-23. doi: 10.1016/j.npep.2008.05.004. Epub 2008 Jul 9.
Corticotropin releasing factor (CRF) is a neuropeptide widely distributed in the brain. The role of CRF in the behavioural activity and modulation of anxiety states in several brain structures has been well documented, but its function in the cerebral cortex still remains unknown. The aim of our study was to investigate the effect of CRF injected bilaterally into rat frontal cortex on the locomotor and exploratory activity and anxiety of rats. We also examined the effect of CRF on extracellularly recorded field potentials in rat frontal cortical slices in vitro. Behavioural experiments showed that CRF in doses of 0.05, 0.1, 0.2 microg/1 microl/site decreased locomotor and exploratory activity during a 40-min session in the open field test. In the elevated plus-maze test, CRF in a dose of 0.2 microg/1 microl/site produced a significant anxiolytic-like effect, which was prevented by CRF receptor antagonists (alpha-helicalCRF(9-41) and NBI 27914). Electrophysiological experiments showed that CRF-induced a transient depression of field potentials in slices partly disinhibited by GABA(A) and GABA(B) receptors antagonists. The blockade of NMDA receptors prevented the occurrence of that effect. The obtained results suggest that CRF may have anxiolytic-like effects in the frontal cortex. Moreover, the peptide inhibits locomotor and exploratory activity and depresses excitatory synaptic transmission in a NMDA receptor-dependent manner.
促肾上腺皮质激素释放因子(CRF)是一种广泛分布于大脑中的神经肽。CRF在多种脑结构的行为活动和焦虑状态调节中的作用已有充分记录,但其在大脑皮层中的功能仍不清楚。我们研究的目的是探讨双侧注射到大鼠额叶皮质的CRF对大鼠运动和探索活动以及焦虑的影响。我们还研究了CRF对体外记录的大鼠额叶皮质切片场电位的影响。行为实验表明,在旷场试验中,剂量为0.05、0.1、0.2微克/1微升/位点的CRF在40分钟内降低了运动和探索活动。在高架十字迷宫试验中,剂量为0.2微克/1微升/位点的CRF产生了显著的抗焦虑样作用,CRF受体拮抗剂(α-螺旋CRF(9-41)和NBI 27914)可阻止这种作用。电生理实验表明,CRF诱导的切片场电位短暂抑制部分被GABA(A)和GABA(B)受体拮抗剂解除抑制。NMDA受体的阻断可防止这种效应的发生。所得结果表明,CRF可能在额叶皮质具有抗焦虑样作用。此外,该肽以NMDA受体依赖的方式抑制运动和探索活动,并抑制兴奋性突触传递。