Spina M G, Basso A M, Zorrilla E P, Heyser C J, Rivier J, Vale W, Merlo-Pich E, Koob G F
Institute for Medical Neurobiology, Otto-von-Guericke University, Magdeburg, Germany.
Neuropsychopharmacology. 2000 Mar;22(3):230-9. doi: 10.1016/S0893-133X(99)00108-6.
Astressin, a novel corticotropin releasing factor (CRF) antagonist, has been found to be particularly potent at inhibiting the hypothalamo-pituitary-adrenal axis. The aim of the present study was to determine the effects in rats of astressin in attenuating the anxiogenic-like response produced by social stress and intracerebroventricular (ICV) CRF administration on the elevated plus-maze, and ICV CRF-induced locomotor activation in the rat. Astressin significantly reversed the anxiogenic-like response induced by both social stress and ICV rat/humanCRF (r/hCRF) on the elevated plus-maze, but failed to block the effects of r/hCRF-induced locomotor activity in a familiar environment. When these results were compared to previous studies performed with the same paradigms using other CRF antagonists, astressin showed effects similar to those of D-PheCRF(12-41) on plus-maze performance. However, contrary to alpha-helicalCRF(9-41) and D-PheCRF(12-41), astressin had no effect on CRF-induced locomotor activity. These results suggest that astressin may have a unique anti-CRF profile compared to previously tested antagonists.
阿斯特瑞辛是一种新型促肾上腺皮质激素释放因子（CRF）拮抗剂，已发现其在抑制下丘脑 - 垂体 - 肾上腺轴方面具有特别强的效力。本研究的目的是确定阿斯特瑞辛对大鼠的影响，即在高架十字迷宫实验中减轻社会应激和脑室内（ICV）注射CRF所产生的焦虑样反应，以及在大鼠中ICV注射CRF诱导的运动激活。阿斯特瑞辛显著逆转了社会应激和ICV注射大鼠/人CRF（r/hCRF）在高架十字迷宫实验中所诱导的焦虑样反应，但未能阻断r/hCRF在熟悉环境中诱导的运动活动效应。当将这些结果与之前使用其他CRF拮抗剂以相同范式进行的研究进行比较时，阿斯特瑞辛在十字迷宫实验表现上显示出与D - PheCRF(12 - 41)相似的效果。然而，与α - 螺旋CRF(9 - 41)和D - PheCRF(12 - 41)不同，阿斯特瑞辛对CRF诱导的运动活动没有影响。这些结果表明，与之前测试的拮抗剂相比，阿斯特瑞辛可能具有独特的抗CRF特性。
