An overview of the behavioral, neurobiological and morphological effects of topiramate in rats exposed to chronic unpredictable mild stress

Abstract

The environmental psychological stress causes depressive disorders. Stress causes many neurobiological, neurodegenerative changes in brain. Topiramate (TPM) is used in the treatment of epilepsy and psychiatric diseases. However, there are conflicting findings that TPM disrupts cognitive functions. We aimed to investigate the effects of TPM on depression, anxiety, learning and memory as well as neurobiological, morphological changes in rats exposed to chronic unpredictable mild stress (CUMS). After CUMS was formed by random application of nine mild stressors for 45 days, TPM (at doses of 0.1, 1, 10, 100 mg/kg) was administered for 21 days. Sucrose preference, locomotor activity, forced swimming, elevated plus maze and Morris water maze tests were performed. Corticosterone, BDNF (Brain-derived neurotrophic factor) and glutamate levels and volumes of hippocampus were evaluated. Body weights of the rats were measured. Immobilization time increased in CUMS, CUMS + TPM0.1 in forced swimming test and time spent in platform quadrant increased in Control + TPM1, CUMS, CUMS + TPM0.1, CUMS + TPM1 in Morris water maze test. Control + TPM1 decreased distance to platform in Morris water maze while CUMS + TPM100 increased. Learning is impaired in CUMS + TPM100 while it is improved in Control + TPM1. BDNF levels increased in CUMS and glutamate levels increased in CUMS, CUMS + TPM10. Body weight decreased in CUMS, CUMS + TPM0.1, CUMS + TPM1, CUMS + TPM100. Hippocampus volumes increased in CUMS. In conclusion, CUMS improved cognition and this finding was supported by the increase of BDNF levels and volume of hippocampus. TPM 1 mg/kg improved cognition in non-stressed rats. TPM 0.1 and 1 mg/kg improved while TPM 100 mg/kg impaired memory in rats exposed to stress.