Skórzewska Anna, Bidziński Andrzej, Hamed Adam, Lehner Małgorzata, Turzyńska Danuta, Sobolewska Alicja, Maciejak Piotr, Szyndler Janusz, Wisłowska-Stanek Aleksandra, Płaźnik Adam
Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland.
Horm Behav. 2008 Nov;54(5):602-12. doi: 10.1016/j.yhbeh.2008.06.002. Epub 2008 Jun 14.
In the present study we have examined the influence of intracerebroventricullary administered CRF, and a non-selective CRF receptor antagonist, alpha-helical CRF((9-41)), on rat conditioned fear response, serum corticosterone, c-Fos and CRF expression, and concentration of amino acids (in vitro), in several brain structures. Pretreatment of rats with CRF in a dose of 1 microg/rat, enhanced rat-freezing response, and further increased conditioned fear-elevated concentration of serum corticosterone. Moreover, exogenous CRF increased aversive context-induced expression of c-Fos in the parvocellular neurons of the paraventricular hypothalamic nucleus (pPVN), CA1 area of the hippocampus, and M1 area of the frontal cortex. A different pattern of behavioral and biochemical changes was present after pre-test administration of alpha-helical CRF((9-41)) (10 microg/rat): a decrease in rat fear response and serum corticosterone concentration; an attenuation of fear-induced c-Fos expression in the dentate gyrus, CA1, Cg1, Cg2, and M1 areas of the frontal cortex; a complete reversal of the rise in the number of CRF immunoreactive complexes in the M2 cortical area, induced by conditioned fear. Moreover, alpha-helical CRF((9-41)) increased the concentration of GABA in the amygdala of fear-conditioned rats. Altogether, the present data confirm and extend previous data on the integrative role of CRF in the central, anxiety-related, behavioral and biochemical processes. The obtained results underline also the role of frontal cortex and amygdala in mediating the effects of CRF on the conditioned fear response.
在本研究中，我们检测了脑室内注射促肾上腺皮质激素释放因子（CRF）以及一种非选择性CRF受体拮抗剂——α-螺旋CRF（9-41），对大鼠条件性恐惧反应、血清皮质酮、c-Fos和CRF表达以及几种脑结构中氨基酸浓度（体外）的影响。用1微克/大鼠剂量的CRF预处理大鼠，增强了大鼠的僵住反应，并进一步提高了条件性恐惧引起的血清皮质酮浓度。此外，外源性CRF增加了下丘脑室旁核小细胞神经元（pPVN）、海马CA1区和额叶皮质M1区中厌恶情境诱导的c-Fos表达。在预先注射α-螺旋CRF（9-41）（10微克/大鼠）后，出现了不同的行为和生化变化模式：大鼠恐惧反应和血清皮质酮浓度降低；额叶皮质齿状回、CA1、Cg1、Cg2和M1区中恐惧诱导的c-Fos表达减弱；条件性恐惧诱导的M2皮质区CRF免疫反应复合物数量增加完全逆转。此外，α-螺旋CRF（9-41）增加了恐惧条件化大鼠杏仁核中γ-氨基丁酸（GABA）的浓度。总之，目前的数据证实并扩展了先前关于CRF在中枢、焦虑相关行为和生化过程中的整合作用的数据。所获得的结果还强调了额叶皮质和杏仁核在介导CRF对条件性恐惧反应影响中的作用。
