Behavioral effects of four antidepressants on an ischemic rat model of emotional disturbances

The aim of this study was to examine the psychopharmacological effects of antidepressants on post-ischemic rats. Global transient cerebral ischemia was performing with the four-vessels occlusion method. Locomotor activity, neurological scores and activity during the 20 min forced swimming test (FST) session were comparatively evaluated in sham-operated and ischemic animals. Three doses of four antidepressants or saline were then intraperitoneally administered 23.5, 5 and 1 h before the 5 min FST session, and 0.5 h before the elevated plus-maze (EPM). Histological quantification of neuronal loss was performed at the end of the experiments. Results show that before treatment, ischemic animals present significantly greater spontaneous motor activity, a neurological score and an immobility time in the 20 min FST lower than sham-operated animals. After treatment, compared to the saline group, we show an antidepressant-like activity in the FST with all the molecules, except with the fluvoxamine, and an anxiolytic-like effect in the EPM, with at least one dose of each compounds. The observed effect is very similar according to whether or not the animals were ischemic, with a tendency to react more important for ischemic animals versus sham-operated. This difference is significant in the FST for the immobility time and in the EPM for the ratio of distance, of time, of number of entrances and non-protected head dips with the 45 mg dose of milnacipran. These results demonstrate that even though global transient cerebral ischemia induces important cerebral lesions, it modifies little the effects of the different antidepressants, whatever their primary pharmacological target, with a particular effectiveness with the dual serotonin and norepinephrine reuptake inhibitor milnacipran. (C) 2009 Elsevier B.V. All rights reserved.