Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
Eur Neuropsychopharmacol. 2022 Apr;57:1-14. doi: 10.1016/j.euroneuro.2021.12.011. Epub 2022 Jan 7.
Anxiety disorders are pervasive psychiatric disorders causing great suffering. The high (HAB) and low (LAB) anxiety-related behaviour rats were selectively bred to investigate neurobiological correlates of anxiety. We compared the level of neuropeptides relevant for anxiety- and depression-related behaviours in selected brain regions of HAB and LAB rats. Increased anxiety and depression-like behaviours of male and female HAB rats in the elevated plus-maze and forced swim tests were accompanied by elevated levels of neuropeptide Y (NPY) in the prefrontal (PFC), frontal (FC) and cingulate cortex (CCx), the striatum, and periaqueductal grey (PAG). Moreover, HAB rats displayed sex-dependent, elevated levels of calcitonin gene-related peptide (CGRP) in PFC, FC, CCx, hippocampus, and PAG. Higher neurokinin A (NKA) levels were detected in CCx, striatum, and PAG in HAB males and in CCx and hypothalamus in HAB females. Increased neurotensin was detected in CCx and PAG in HAB males and in hypothalamus in HAB females. Elevated corticotropin-releasing hormone (CRH) levels appeared in female HAB hypothalamus. Significant correlations were found between anxiety-like behaviour and NPY, CGRP, NKA, and neurotensin, particularly with NPY in CCx and striatum, CGRP in FC and hippocampus, and NKA in entorhinal cortex. This is the first report of NPY, CGRP, NKA, Neurotensin, and CRH measurements in brain regions of HAB and LAB rats, which showed widespread NPY and CGRP alterations in cortical regions, with NKA and neurotensin changes localised in sub-cortical areas. The results may contribute to elucidate pathophysiological mechanisms underlying anxiety and depression and should facilitate identifying novel therapeutic targets.
焦虑症是一种普遍存在的精神疾病，会给患者带来极大的痛苦。高焦虑（HAB）和低焦虑（LAB）相关行为大鼠被选择性繁殖，以研究焦虑相关的神经生物学相关性。我们比较了 HAB 和 LAB 大鼠选定脑区与焦虑和抑郁相关行为相关的神经肽水平。雄性和雌性 HAB 大鼠在高架十字迷宫和强迫游泳试验中的焦虑和抑郁样行为增加，伴有前额叶（PFC）、额前皮质（FC）和扣带皮质（CCx）、纹状体和中脑导水管周围灰质（PAG）中神经肽 Y（NPY）水平升高。此外，HAB 大鼠还表现出性别依赖性的 PFC、FC、CCx、海马和 PAG 中降钙素基因相关肽（CGRP）水平升高。HAB 雄性大鼠的 CCx、纹状体和 PAG 以及 HAB 雌性大鼠的 CCx 和下丘脑检测到更高水平的神经激肽 A（NKA）。HAB 雄性大鼠的 CCx 和 PAG 以及 HAB 雌性大鼠的下丘脑检测到神经降压素升高。HAB 雌性大鼠的下丘脑出现促肾上腺皮质激素释放激素（CRH）水平升高。在焦虑样行为与 NPY、CGRP、NKA 和神经降压素之间发现了显著相关性，尤其是在 CCx 和纹状体中的 NPY、FC 和海马中的 CGRP 以及内嗅皮质中的 NKA。这是首次在 HAB 和 LAB 大鼠的脑区中测量 NPY、CGRP、NKA、神经降压素和 CRH，显示皮质区域广泛存在 NPY 和 CGRP 改变，NKA 和神经降压素改变局限于皮质下区域。这些结果可能有助于阐明焦虑和抑郁的病理生理机制，并有助于确定新的治疗靶点。
