A Review of the Potential Receptors of Migraine with a Special Emphasis on CGRP to Develop an Ideal Antimigraine Drug

Naduchamy, Krishna P; Parthasarathy, Varadarajan

doi:10.2174/1874467213999200824124532

Cited by 6 publications

(1 citation statement)

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“…The CGRP is distributed in the peripheral and central nervous system, including the hypothalamus, central gray matter, amygdala, hippocampus, and dentate gyrus (Skofitsch & Jacobowitz, 1985). Because it has been reported that CGRP is released from the trigeminal terminal in an animal model of migraine, accumulating evidence indicates that CGRP is a major contributor to the onset of migraine (Deen et al, 2017;Iyengar et al, 2019;Naduchamy & Parthasarathy, 2020). However, experimental evidence exists that supports the role of CGRP in depressive-like behavior.…”

Section: Introductionmentioning

confidence: 99%

CGRP overexpression does not alter depression-like behavior in mice

Hashikawa-Hobara¹,

Otsuka²,

Okujima³

et al. 2021

PeerJ

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Background The calcitonin gene-related peptide (CGRP) is a neuropeptide that is released from capsaicin-sensitive nerves as a potent vasodilator involved in nociceptive transmission. While CGRP has been rigorously studied for its role in migraines owing to its vasodilation and inflammation activities, the effects of CGRP overexpression on depressive-like behaviors remain insufficiently understood. Methods In the present study, we performed a battery of behavioral tests, including the social interaction test, open field test, and sucrose preference test, to evaluate social defeat stress using male C57BL6J or CGRP overexpression in transgenic (Tg) mice (CGRP Tg). We performed mRNA and protein analyses on the brain-derived neurotrophic factor (BDNF), phosphorylated Akt, mTOR, and p70S6K in the hippocampi. Results CGRP Tg mice showed increased levels of Bdnf mRNAs, low locomotor activity, and no deficits in social interaction, which indicate that CGRP Tg mice exhibit stress resistance and not depression. However, the open field test significantly decreased after 15-day social defeat stress exposure. We also evaluated depressive-like behavior using the sucrose preference and social interaction tests. Our data indicate that defeated CGRP Tg mice exhibited a depressive-like phenotype, which was inferred from increased social avoidance and reduced sucrose preference compared with non-defeated controls. Although stress exposure did not change the BDNF levels in CGRP Tg mice, it significantly decreased the expression levels of p-Akt, p-mTOR and p-p70S6K in the mice hippocampi. We conclude that CGRP-overexpressing Tg mice have normal sensitivity to stress and down-regulated hippocampal Akt/mTOR/p70S6K pathways.

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