bi-3-azaoxoisoaporphine derivatives have antidepressive properties in a murine model of post stroke-depressive like behavior.

In the present study, three bi-3-azaoxoisoaporphine derivatives were synthesized and intracerebroventricularly administrated to BALB/c mice. The antidepressant actions in stroke-induced depressive like behavior in mice were examined using despair swimming test and tail suspension test. The results reported that bilateral common carotid arteries occlusion caused a significant abnormality of the normal behaviors. Behavioral models demonstrated that synthesized compounds showed antidepressant action. The most antidepressant active compound was DIME2 (4,4'-dimethyl-7H,7'H- [6,6'-bibenzo[e]perimidine]-7,7'-dione), which decreased the immobility time and increased the swimming and climbing times in despair swimming model. DIME2 also showed similar results in decreasing the immobility time in the tail suspension model. In open field tests, DIME2 at 0.1 μg/μl showed a significant activity in the modification of the distance movement and the number and duration of rearing versus bilateral common carotid arteries occlusion (P<0.001). Furthermore, bilateral common carotid arteries occlusion caused a significant increase in the water consumption and significant decreasing in the sucrose consumption which are indicated as a state of anhedonia, a well known common symptom of transient ischemic stroke-induced depressive like behavior, versus normal group (P<0.001). In conclusion, bi- 3-azaoxoisoaporphine derivatives can be considered as antidepressant agents for post stroke-induced depressive like behavior therapy.