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 1h before the 5 min FST session, and 0.5h 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.