PURPOSE: Histamine H3 receptor ligands may have antidepressant and anxiolytic 
effects. They can also compensate for metabolic disorders, which affect glucose 
or triglyceride levels. In previous studies, we have shown that pitolisant, a 
histamine H3 receptor antagonist/inverse agonist and σ1 receptor agonist, 
prevented the development of certain metabolic and depressive-like disorders in 
mice that have been treated chronically with olanzapine.
METHODS: As a continuation of our previous experiments, this study aimed to 
investigate the antidepressant- and anxiolytic-like activity of pitolisant in 
mice using the corticosterone-induced depression model. The forced swim and the 
elevated plus maze tests were used as behavioral endpoints. We also studied the 
effect pitolisant had on the level of acetoacetic acid in the urine as well as 
the glucose tolerance and body weight of the mice that had been administered 
corticosterone.
RESULTS: Pitolisant (10 mg/kg b.w.) did not prevent depressive-like behavior in 
mice during the chronic corticosterone administration but did counteract 
anxiety-like behavior, whilst fluoxetine (10 mg/kg) was shown to protect the 
mice from both of these behaviors. None of the treatments that were used in the 
study showed an effect on the locomotor activity of the mice. Pitolisant did not 
prevent an increase in acetoacetic acid levels in the urine, nor did it improve 
glucose tolerance in the tested mice.
CONCLUSION: Although literature data indicates that there is significant 
potential for finding an antidepressant and anti-diabetic drug among the 
histamine H3 and σ1 receptor ligands, in our study, pitolisant was shown to only 
slightly compensate for corticosterone-induced abnormalities. However, further 
research will be required to study pitolisant's anxiolytic-like activity.