Effects of brain biogenic amines on ethanol withdrawal reactions and the development of ethanol dependence in mice

Mice were made physically dependent on ethanol by a four-day period of ethanol inhalation. A single injection of L-dopa tended to enhance ethanol withdrawal reactions and 5HTP tended to suppress it. Daily treatment with PCPA and L-dopa or pretreatment with 6OHDA tended to modify the severity of withdrawal reactions. PCPA slightly decreased the severity, 6OHDA tended to aggravate the severity, and L-dopa tended to decrease the severity. The simultaneous estimation of brain biogenic amine levels suggests that 5HT and DA may be involved in the development of physical dependence on ethanol. Treatment with neuropharmacological drugs during ethanol withdrawal modified the severity of ethanol withdrawal reactions. Pentobarbital and diazepam completely suppressed ethanol withdrawal reactions. GHBA and reserpine suppressed the severity and haloperidol, imipramine, and methylphenidate aggravated it. The simultaneous estimation of brain catecholamine levels suggests that suppression of ethanol withdrawal reactions consistently results from the decreased activities of either noradrenergic or dopaminergic neurons. However, the effects of biogenic amines on ethanol withdrawal reactions may be different from those on the development of physical dependence on ethanol.