Melatonin Alleviates Valproic Acid-Induced Memory Impairments in Adult Rats

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Anusara Aranarochana
Suchada Krutsri
Kornrawee Suwannakot
Pornthip Chaisawang
Wanassanun Pannangrong
Jariya Umka Welbat


Background and objectives: Valproic acid is a broad-spectrum drug widely used as an anticonvulsant. A recent study has indicated that valproic acid reduces gene transcription mediated by inhibition of histone deacetylase activities and contribute to suppression of neural stem cell proliferation, which might help to explain the cause of memory impairment produced in patients and rodents. Melatonin is a hormone secreted by the pineal gland and regulates the circadian rhythm. Previous studies have reported that melatonin exerts antioxidant and neuroprotective properties. It also prevents memory impairment in animal models.  The present study aimed to investigate protective effects of melatonin on memory impairment caused by valproic acid in adult rats.

Methods: Male Spraque-Dawley rats were divided into 6 groups, including control, valproic acid, melatonin, preventive, recovery and throughout groups. Rats received valproic acid (300 mg/kg) twice a day for 14 days or melatonin (8 mg/kg/day) for 14 days (melatonin group) or co-treatment of VPA and melatonin by receiving melatonin during or after valproic acid administration for 14 days (preventive and recovery groups) and 28 days (throughout group). Novel object location and novel object recognition tests were used to assess spatial and non-spatial memories, respectively. Data from the behavioral tests were calculated and converted to discrimination index. 

Results: In novel object location and novel object recognition tests before drug administration, the total exploration times and discrimination index showed no significant different among groups (p>0.05). After drug administration, the total exploration times showed no significant different among groups (p>0.05). In contrast, the discrimination index was significantly higher than zero in control, melatonin, preventive, and throughout groups (p<0.05) but not significantly different from zero in valproic acid-treated and recovery groups (p>0.05).

Conclusion: Melatonin can prevent and improve spatial and non-spatial memory impairments caused by valproic in adult rats.


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