Neuropeptide Y, calcitonin gene-related peptide, and neurokinin A in brain regions of HAB rats correlate with anxiety-like behaviours

• Published in: European neuropsychopharmacology Vol. 57; pp. 1 - 14
• Main Authors: Carboni, Lucia, El Khoury, Aram, Beiderbeck, Daniela I., Neumann, Inga D., Mathé, Aleksander A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2022
• Subjects: Animals; Anxiety; Anxiety Disorders; Brain - metabolism; Calcitonin Gene-Related Peptide - metabolism; CGRP; Corticotropin releasing hormone; Female; HAB LAB rats; Male; Neurokinin A; Neurokinin A - metabolism; Neuropeptide Y - metabolism; Neurotensin; NPY; Rats; Corticotropin releasing hormone; HAB LAB rats; Neurotensin; Neurokinin A; CGRP; NPY
• ISSN: 0924-977X; 1873-7862; 1873-7862
• DOI: 10.1016/j.euroneuro.2021.12.011

•HAB rats show higher neuropeptide levels in distinct brain areas with sex differences.•NPY and CGRP alterations are widespread, mainly involving cortical regions.•NKA and neurotensin changes are more restricted and localised in sub-cortical areas.•CRH levels are specifically increased in the hypothalamus of HAB females.•Significant correlations exist between anxiety-like behaviour and neuropeptide levels. 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.