Aripiprazole (APZ) is regarded as a first-line atypical
antipsychotic used for the treatment of first and multiple episodes of
schizophrenia to improve positive- and negative-symptoms. Its therapeutic indications were extended to acute manic and mixed episodes associated with
bipolar disorder. In addition, APZ was approved as an adjunct
therapy for
major depressive disorder in 2007. Compared to other
antipsychotic drugs, APZ has a unique pharmacological profile. It is a partial agonist at D₂
dopamine receptors and
serotonin 5-HT(1A) and 5-HT₇ receptors, whereas it is an antagonist at
serotonin 5-HT(2A) and 5-HT₆ receptors. Since
epilepsy is often accompanied with neurological comorbidities such as depression, anxiety and cognitive deficits caused by both the disease and/or drug treatment, we wished to examine the effects of a sub-chronic treatment (>14 consecutive days) with APZ (0.3, 1 and 3 mg/kg; i.p.) on both absence
seizures and WAG/Rij rat's behavior using different standard paradigms: Open field (OF) test, elevated plus maze (EPM) test, forced swimming (FS) test,
sucrose consumption (SC) test and Morris water maze (MWM). WAG/Rij rats represent a validated genetic animal model of
absence epilepsy with mild-depression comorbidity, also including other behavioral alterations. APZ treatment showed some anti-absence properties and regarding the behavioral comorbidity in this rat strain, we observed that APZ possesses clear
antidepressant effects in the FS and SC tests also increasing memory/learning function in the Morris water maze test. In the two anxiety models used, APZ showed only minor effects. In conclusion, our results indicate that APZ might actually have a potential in treating absence
seizures or as add-on
therapy but more interestingly, these effect might be accompanied by positive modulatory actions on depression, anxiety and memory which might be also beneficial in other
epileptic syndromes. This article is part of a Special Issue entitled '
Cognitive Enhancers'.