Jahn H, Montkowski A, Knaudt K, Ströhle A, Kiefer F, Schick M, Wiedemann K
University of Hamburg, Department of Psychiatry and Psychotherapy, Martinistr. 52, 20251 Hamburg, Germany.
Brain Res. 2001 Mar 2;893(1-2):21-8. doi: 10.1016/s0006-8993(00)03275-3.
Previously we have shown that atrial natriuretic peptide (ANP) has anxiolytic-like properties after intraperitoneal, intracerebroventricular and intraamygdala infusion in rats. Since C-type natriuretic peptide (CNP) exerts endocrine and behavioral effects opposing those of ANP, we characterized the behavioral properties of CNP after icv infusion in rats by their performance in the elevated plus maze with and without the corticotropin-releasing hormone (CRH) antagonist alpha-helical-CRH (alpha-CRH). Low CNP doses of 0.05 microg icv or 0.1 microg icv did not significantly influence the behavior of rats in the plus maze. At higher doses (0.5 microg, 2 microg, 5 microg icv) CNP had distinct anxiogenic properties. Our hypothesis that corticotropin-releasing hormone (CRH) is involved, which elicits anxiety-like behavior, was examined by icv coadministration of alpha-CRH, an antagonist at CRH-1 and CRH-2-receptors. Icv alpha-CRH alone had no intrinsic anxiolytic properties at a dose of 25 microg. The anxiogenic effects of 2 microg CNP icv seen in the plus maze were entirely blocked by alpha-CRH. Directly after exposition ACTH and corticosterone levels did not differ between the groups, but after 30 min ACTH levels were significantly higher in the CNP-treated group compared to alpha-CRH/CNP-treated animals. Corticosterone was found significantly lowered in the alpha-CRH/saline group compared to the CNP treated group but not compared to saline controls. Our data suggest opposing effects of CNP and ANP on anxiety-related behavior and neuroendocrine regulation in rats, which appear to be mediated via different receptor occupation and brain regions, and by a CRH-dependent mechanism.
此前我们已经表明，心房利钠肽（ANP）在大鼠腹腔内、脑室内和杏仁核内注射后具有抗焦虑样特性。由于C型利钠肽（CNP）产生的内分泌和行为效应与ANP相反，我们通过大鼠在有和没有促肾上腺皮质激素释放激素（CRH）拮抗剂α-螺旋CRH（α-CRH）的高架十字迷宫中的表现，来表征脑室内注射CNP后的行为特性。脑室内注射0.05微克或0.1微克的低剂量CNP对大鼠在十字迷宫中的行为没有显著影响。在较高剂量（脑室内注射0.5微克、2微克、5微克）时，CNP具有明显的致焦虑特性。我们关于促肾上腺皮质激素释放激素（CRH）参与引发焦虑样行为的假设，通过脑室内共同注射α-CRH（一种CRH-1和CRH-2受体拮抗剂）进行了检验。单独脑室内注射25微克的α-CRH没有内在的抗焦虑特性。在十字迷宫中观察到的脑室内注射2微克CNP的致焦虑效应被α-CRH完全阻断。暴露后立即检测，各组之间促肾上腺皮质激素（ACTH）和皮质酮水平没有差异，但30分钟后，与α-CRH/CNP处理的动物相比，CNP处理组的ACTH水平显著更高。与CNP处理组相比，α-CRH/生理盐水组的皮质酮水平显著降低，但与生理盐水对照组相比没有差异。我们的数据表明，CNP和ANP对大鼠焦虑相关行为和神经内分泌调节具有相反的作用，这似乎是通过不同的受体占据和脑区，以及一种依赖CRH的机制介导的。
