The role of calcitonin gene-related peptide in post-stroke depression in chronic mild stress-treated ischemic rats.

Poststroke depression (PSD) is the most common psychological sequel after stroke. Although the neurological mechanisms of PSD remain to be fully elucidated, numerous studies have implicated the calcitonin gene-related peptide (CGRP), a potent vasodilatory neuropeptide, as key modulator of the depression. A PSD rat model, which was established by middle cerebral artery occlusion (MCAO) and following chronic unpredictable mild stress (CUMS) procedures, was used to investigate the role of CGRP in post-stroke mood disturbances. In the present study, depressive-like state such as anhedonia and behavioral despair was found in CUMS-treated ischemic rat, as measured by sucrose preference test, open-field test and forced swimming test. Moreover, CGRP immunoreactivity (CGRP-ir) concentration in CSF and hippocampus were increased in the PSD rats, compared to the MCAO or CUMS subjects. The other separate groups were implanted chronically with unilateral cannulae in the lateral cerebral ventricle. GABA and its receptor antagonist αGABA(8-37) were administrated centrally into ischemic and PSD rats, respectively. Administration of CGRP into the ischemic rat increased depression-like behaviors in a dose-dependent manner, whereas icv infusion of αCGRP(8-37) produced antidepressant effects in PSD rats, implying that the PSD is mediated, at least partially, by endogenous CGRP receptor activation. Taken together, these results suggest a pivotal role for central CGRP signaling in the modulation of PSD.