The investigation of antidepressant and anxiolytic effects of pregabalin and its mechanisms of action in rats.

OBJECTIVES: Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and neuropathic pain patients. PGB is often combined with anxiolytics and antidepressants. We aimed to investigate the antidepressant and anxiolytic effects of PGB and compare its effects with those of antidepressant and anxiolytic drugs and their combined use. METHODS: Wistar Albino rats were used, and PGB (5, 10, 20, and 40 mg/kg), amitriptylin (AMT), fluoxetine (FLX), ketamine (KET), and diazepam (DZM), as well as combinations of PGB (20 mg/kg) with AMT, FLX, KET, and DZM, were administered. Elevated plus maze, forced swimming, and locomotor activity tests were performed. RESULTS: In the elevated plus maze, PGB10, 20, 40, AMT, FLX, and DZM increased open arm time. The PGB20+FLX combination increased compared to PGB20. In forced swimming, PGB doses increased immobility time. AMT, FLX, DZM, and KET decreased compared to control and PGB doses. Other combinations of PGB20 reversed immobility time, except FLX. In locomotor activity, PGB20, AMT, KET, and DZM decreased distance. CONCLUSION: PGB had a depressant effect in all doses and a dose-dependently anxiolytic effect. In combinations of PGB with AMT, KET, and DZM, it reversed their antidepressant effects. We assumed FLX could be preferred instead of AMT in patients using PGB. When PGB is used in combination, drug interactions should be considered. These results are also very remarkable in terms of pharmacoeconomics.

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

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.