The Investigation of Valproic Acid Administration on Learning, Social Interaction, and Depression Induced by Withdrawal Syndrome in Morphine-Depended Mice

Abstract

Opioid addiction causes mood disorders and increases anxiety, depression, and cognitive impairment. Valproate exerts a neuroprotective effect preventing damage and neural degeneration in epilepsy. The animals were randomly divided into four groups (n=6). The control and valproic acid (VPA) groups were injected intraperitoneally with saline or valproic acid respectively. In the morphine sulfate (MOR) group, animals were injected subcutaneously with morphine sulfate. The MOR + VPA group received two injections of drugs, valproate, and morphine, as well as the VPA and MOR groups. All intraperitoneal and subcutaneous injections were done for 8 days. The animals were assessed on day 8 to behavioral tests. The administration of valproic acid and morphine was discontinued from day 8 and the animals entered spontaneous withdrawal syndrome. The behavioral tests were repeated on day 11. Results showed that PI% decreased in NORT in the VPA, MOR, and MOR + VPA groups compared with the CTL group in the withdrawal phase. The concomitant administration of VPA and morphine caused an increase in social interaction criteria in both the chronic and withdrawal phases. The decrease in immobility time of the VPA and MOR + VPA groups compared to the CTL group in the withdrawal phase was not statistically significant in the tail suspension test. The VPA can be assessed based on the degree of anxiety and depressive behaviors caused by the withdrawal syndrome. Therefore, reducing stress in rats during morphine withdrawal may be part of the beneficial effects of VPA in improving social relationships and depression indices.