Vanillin attenuates the ethanol withdrawal syndrome and ethanol withdrawal induced anxiety by regulating the neurochemical balance

Ethanol abuse is a major public issue globally and withdrawal of ethanol after chronic exposure contributes to the development of behavioural changes. The present study evaluates vanillin effect against the ethanol withdrawal syndrome (EWS) and the associated anxiety. Rats were exposed to ethanol for 21 days at 7.2% concentration maximum with drinking water in a modified liquid diet. Vanillin at doses of 100 and 200 mg/kg were administered 30 min prior to ethanol withdrawal, and behavioural changes were observed at 1st, 2nd, 4th, 6th and 12th h of ethanol withdrawal. Moreover, the locomotor activity was assessed using the astrophotometer and level of anxiety by the elevated plus maze. The level of neurotransmitters and mRNA expression of corticotropin-releasing factor (CRF) and corticotropin releasing factor receptor 1 (CRFR1) were estimated in brain tissue of vanillin treated EWS rats. There was a significant improvement in the ethanol withdrawal behaviour in the vanillin treated group compared to EWS rats. The locomotor activity and level of anxiety was observed to be reduced significantly (p < 0.01) in the vanillin treated group compared to EWS rats. Treatment with vanillin ameliorates the altered level of gamma-aminobutyric acid (GABA), dopamine and glutamate and level of corticosterone in ethanol withdrawal rats. mRNA expression of CRF and CRFR1 was reduced significantly (p < 0.01) in brain tissue of the vanillin treated group compared to the EWS group of rats. In conclusion, data reveal that treatment with vanillin shows a beneficial effect against EWS and ethanol withdrawal associated anxiety by regulating CRF/CRFR1 expression.