Ohmura Yu, Yamaguchi Taku, Futami Yukino, Togashi Hiroko, Izumi Takeshi, Matsumoto Machiko, Yoshida Takayuki, Yoshioka Mitsuhiro
Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, N15 W7 Kita-ku, Sapporo, 060-8638, Japan.
Behav Brain Res. 2009 Mar 17;198(2):429-33. doi: 10.1016/j.bbr.2008.11.025. Epub 2008 Nov 24.
Previous studies have shown that psychological stress affects attentional function, and corticotropin releasing factor (CRF) is closely related to stress responses. In the present study, we examined the effect of CRF on attentional function using a five-choice serial reaction time task (5-CSRTT) in rats. Accuracy in the 5-CSRTT was used as the index of attentional function. Human/rat CRF was intracerebroventricularly injected (0, 0.01, 0.1, or 1 microg/5 microl saline) 20 min before the beginning of the test trial in male Lister hooded rats that generally show high performance in the 5-CSRTT. As a result, 0.1 microg of CRF, but not other doses of CRF, increased accuracy in the 5-CSRTT. However, 0.1 microg of CRF did not affect impulsivity, motivation/appetite, perseverative tendency, or motor function. Even when Wistar rats, which generally show poor performance in the 5-CSRTT were used, 0.1 microg of CRF increased accuracy in the 5-CSRTT. However, the effect of CRF was not significantly attenuated by intracerebroventricular injection of the CRF(1) receptor antagonist antalarmin (5 microg). These results showed that CRF selectively enhances attentional function regardless of baseline attentional performance and rat strain, but this effect may be due to the pathways other than CRF(1) receptors. The present results suggest that CRF is involved in stress-related changes of attention and indicate that moderate stress, but not severe stress, may enhance attentional performance. Furthermore, these findings also indicate that the CRF-related substance could be a target for the development of an agent to improve attentional function.
先前的研究表明,心理压力会影响注意力功能,促肾上腺皮质激素释放因子(CRF)与应激反应密切相关。在本研究中,我们使用大鼠的五选择连续反应时任务(5-CSRTT)来检测CRF对注意力功能的影响。5-CSRTT中的准确性被用作注意力功能的指标。在雄性利斯特帽状大鼠(其在5-CSRTT中通常表现良好)的测试试验开始前20分钟,经脑室注射人/大鼠CRF(0、0.01、0.1或1微克/5微升生理盐水)。结果显示,0.1微克的CRF可提高5-CSRTT的准确性,而其他剂量的CRF则无此作用。然而,0.1微克的CRF并不影响冲动性、动机/食欲、持续性倾向或运动功能。即使使用在5-CSRTT中通常表现较差的Wistar大鼠,0.1微克的CRF也能提高5-CSRTT的准确性。然而,经脑室注射CRF(1)受体拮抗剂安他拉明(5微克)后,CRF的作用并未显著减弱。这些结果表明,CRF可选择性增强注意力功能而不受基线注意力表现和大鼠品系的影响,但这种作用可能是通过CRF(1)受体以外的途径介导的。目前的结果表明,CRF参与了与应激相关的注意力变化,并提示适度应激而非严重应激可能会增强注意力表现。此外,这些发现还表明,与CRF相关的物质可能成为开发改善注意力功能药物的靶点。