Increase In Hepatic Quinolinic Acid Concentrations In Alcohol Withdrawn Rats.

BACKGROUND: Behavioral associated disturbance involves excitotoxic quinolinate in alcohol withdrawal syndrome in man due to increase availability of tryptophan. In present study we investigated alcoholism related clinical features in relation to tryptophan and 5-HT levels in rat's model. METHODS: Locally bred male Wistar rats, weighing 200-250 g were housed separately into 6 animals/ group with 12 h light: dark cycle at room temp 22±3 °C. They were given diet ad libitum, for three days then alcohol 8% (v/v) was added into the liquid diet. Matched control rats of each group were given maltose-dextrin as a substitute of alcohol. Alcohol withdrawal syndrome was assessed after 7 hours by replacing the alcohol-containing liquid diet with tap water. RESULTS: Alcohol withdrawal group showed significant increase (p<0.001) in holo, apo, and total tryptophan 2, 3 dioxygenase enzyme activities, no significant change in brain tryptophan and 5HIAA however significant decrease (p<0.001) in brain 5HT was observed when compared with chow controls. Both alcohols administered and withdrawal groups showed significant rise in serum corticosterone by p<0.05 and p<0.001 respectively. Liver quinolinic acid concentrations were increased significantly (p<0.01) with robust increase in alcohol withdrawn rats. CONCLUSIONS: We conclude that the excitotoxin tryptophan metabolite quinolinic acid of peripheral origin plays significant role in the behavioral manifestation of the alcohol withdrawal syndrome. Tryptophan metabolites should be targeted to develop new strategies in the progress of pharmacological interventions related to alcoholism.

Chronic administration of St. John's Wort attenuates alcohol intake and brain indoleamine 2, 3-dioxygenase activity in mice.

Present study aims to elucidate the effects of chronic administration of St. John's Wort (SJW) (500mg/kg) on brain tryptophan (TRP) metabolites and indoleamine 2-3 dioxygenase (IDO) activity in alcohol treated mice. Locally bred Albino BALB/c mice, weighing 20-25g were divided into three groups (untreated controls, Alcohol, Alcohol +Drug) having 6 mice in each. Freshly prepared ethanol solution was administered in drinking water in the proportion of 5% for three days or 8% for 3 weeks to two groups. After 3 weeks drug group was treated with SJW (dissolved in ethanol: saline 1:3 v/v) at a dose of 500mg/kg was administered orally for 1 week. During treatment alcohol intake was monitored .In present finding chronic administration of SJW significantly reduced ethanol intake by 78.6% (P<0.001) in mice. Data analyzed by student's t-test indicates that SJW remarkably reduce kynurenine (KYN) by 60.9% (P<0.001) and KYN/TRP ratio (IDO) activity) by 70.9% (P<0.001) in brain. Low serotonin level promotes alcohol intake. Presentresults suggest that SJW decreases alcohol intake by inhibiting IDO thereby shifting TRP catabolism towards serotonin synthesis.