Establishment of rat model of post-stroke depression and the effects of citalopram on behavior thereof

Abstract

To establish an animal model of post-stroke depression (PSD) and assess the effects of citalopram on PSD. Fifty-two male SD rats were randomly divided into 3 groups. Normal group (n = 6) underwent sham operation. Chronic unpredictable mild stress (CMS) group (n = 6), underwent separate raising and CMS. Middle cerebral artery occlusion (MCAO) group (n = 24) underwent MCAO and then re-divided into 3 equal subgroups: stroke subgroup, PSD model subgroup (undergoing isolated raising and CMS so as to establish PSD models), and citalopram subgroup (treated with intraperitoneal injection of citalopram, a selective serotonin reuptake inhibitor for 6 weeks). The rats were examined dynamically at the 19th, 28th, and 42nd days after CMS by open-field test (OFT) and sucrose consumption test. On the 19th day after CMS the locomotor activity score of the PSD models was significantly lower (P < 0.001 compared to the baseline level of the same subgroup and to those of the control and stroke rats, P < 0.01 compared to the CMS group); and the frequency of rearing score of the PSD models was significantly decreased (P < 0.001 compared to its baseline level and to those of the control and stroke groups, and P < 0.05 compared to the CMS group). During the days 19 - 42, the frequency of locomotor and exploratory activities of the PSD model rats declined continually, from 37.8 +/- 1.7 to 34.2 +/- 1.2 and from 9.7 +/- 0.8 to 7.8 +/- 0.8 respectively, showing a tendency in just the reverse direction in the CMS group (from 41.0 +/- 1.3 to 42.3 +/- 0.8 and from 11.2 +/- 0.4 to 11.7 +/- 0.8 respectively). The PSD rats showed a reduction in sucrose preference at week 3 and afterwards (P < 0.001 compared with other groups). The levels of open-field activities and proportion of rats with sucrose preference in the citalopram subgroup were all significantly higher than those in other groups (all P < 0.001). Anhedonia and underactivity, the core symptoms in the PSD patients, can be found completely and persistently in the PSD rats. With good operability and repeatability, the PSD rat model is an ideal model for PSD research. Citalopram can improve the behavior abnormality in PSD.