Striatal and hypothalamic neurotransmitter changes during ethanol withdrawal in mice

Abstract

The alterations in striatal and hypothalamic GABA, DA and its metabolites DOPAC and HVA, and in hypothalamic NE were investigated immediately after ethanol removal and during the withdrawal phase following 10 or 30 days of chronic ethanol administration. After 10 days of ethanol, GABA levels were increased immediately after ethanol removal in both the corpus striatum and the hypothalamus. The concentration of striatal DA was increased at days 2 and 3 of withdrawal and was unchanged at any other time. There was no change in the concentration of DOPAC and HVA in the hypothalamus at any time during withdrawal. Striatal DOPAC and HVA levels were increased only at day 7 of withdrawal after 10 and 30 days of ethanol feeding which was associated with a return of striatal DA to control levels. The concentration of NE in the hypothalamus was increased at days 1, 2 and 7 of withdrawal. After 30 days of ethanol, striatal GABA was increased only at day 7 of withdrawal whereas striatal DA levels were only increased at days 2 and 3 of withdrawal. Hypothalamic NE was markedly increased at days 2, 3 and 7 of withdrawal. The increase in DA concentration associated with no change in DOPA accumulation following inhibition of DOPA decarboxylase and a decrease in the striatal disappearance of DA after alphamethylparatyrosine (alpha-MT) suggests the presence of a hypodopaminergic state. On the other hand an increase in the disappearance of NE in the hypothalamus after alpha-MT suggests an increased NE turnover and a hyperadrenergic state during withdrawal. The increase in striatal GABA at day 7 of withdrawal after 30 days of ethanol may be a rebound phenomenon and may reflect the presence of a hypogabaergic state which has been shown to occur during ethanol withdrawal.