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Clozapine is protective against suicide, whereas haloperidol is associated with depressive symptoms. To better understand the pathophysiology of these phenomena, researchers conducted an animal study.
Rats underwent chronic mild stress (CMS; e.g., food was visible but inaccessible) for 7 weeks and began clozapine, haloperidol, or saline (control) at week 4. CMS was associated with behavioral anhedonia (decreased sucrose preference), behavioral despair (immobility rather than swimming in water), and decreases in neuroplasticity. Compared with saline, clozapine reversed the CMS-related deficits, resulting in fewer depression-like manifestations, increased neurogenesis and neuronal survival in the hippocampus, and increased dendritic arborizati…