Behavioural consequences of ethanol withdrawal: role of the tryptophan pathway
Alcohol, Abstinence, Rat, Anxiety, Depression, Kynurenine
Anxiety and depression are symptoms associated with ethanol withdrawal that lead individuals to relapse. In the kynurenine pathway the enzyme indoleamine 2,3 dioxygenase (IDO) is responsible for the conversion of tryptophan to kynurenine and a dysregulation of this pathway has been associated with psychiatric disorders, such as anxiety and depression. The present study evaluated the early and late behavioural and biochemical effects of ethanol withdrawal in rats. Male Wistar rats were submitted to increasing concentrations of ethanol during 21 days as the only source of liquid diet. In the experiment 1, both control and withdrawn groups were submitted to a battery of behavioural tests 3, 5, 10, 19 and 21 days following ethanol removal. In the experiment 2, animals were euthanized 3 days (short-term) or 21 days (long-term) after withdrawal and the brains were dissected altogether, following kynurenine concentration analysis in prefrontal cortex, hippocampus and striatum. Short-term ethanol withdrawal decreased the exploration of the open arms in the elevated plus maze. In the forced swimming test, long-term ethanol withdrawn rats displayed higher immobility time than control animals. Ethanol withdrawal altered neither locomotion nor motor coordination of rats. In the experiment 2, kynurenine concentrations were increased in the prefrontal cortex after a long-term period of withdrawal. In conclusion, short-term ethanol withdrawal produced anxiety-like while long-term withdrawal induced depressive-like behaviours. Long-term ethanol withdrawal elevated kynurenine levels specifically in the prefrontal cortex, suggesting that the depressive-like responses observed after long-term withdrawal might be related to the increased IDO activity.