Opposite changes in turnover of noradrenaline and dopamine in the CNS of ethanol-dependent mice.
Turnover rates of noradrenaline and of dopamine were examined in regions of the CNS (brainstem, frontal cortex, hippocampus, striatum) and in cardiac tissue of mice that had ingested ethanol for 2 or 7 days and during withdrawal of ethanol. Turnover of neurotransmitters was assessed from the accumulation of dihydroxyphenylalanine and from the depletion in levels of noradrenaline, dopamine and their deaminated metabolites in tissue, after irreversible inhibition of aromatic L-amino acid decarboxylase with DL-alpha-monofluoromethyldopa. There were no consistent changes in the turnover of noradrenaline or dopamine after 2 or 7 days of continuous ingestion of ethanol, but at the time that animals exhibited peak ethanol-withdrawal symptoms (8 hr after ethanol consumption was stopped), the turnover of dopamine in the striatum was markedly decreased to less than a third of that observed in control animals, whereas the turnover of noradrenaline in the brainstem was increased by a half. The changes in turnover of neurotransmitters in specific regions of the brain may reflect alterations in neuronal activity that result from withdrawal of ethanol, or may be determinants of particular ethanol-withdrawal symptoms.
Eisenhofer
G
G
Clinical Neuroscience Branch, NINCDS, National Institutes of Health, Bethesda, Maryland 20892.
Szabo
G
G
Hoffman
P L
PL
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008750:Methyldopa / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*
D002395:Catecholamines; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine; D009638:Norepinephrine