CHRONIC ETHANOL TREATMENT LEADS TO INCREASED ORNITHINE DECARBOXYLASE ACTIVITY - IMPLICATIONS FOR A ROLE OF POLYAMINES IN ETHANOL DEPENDENCEAND WITHDRAWAL

Recent research has focused on the N-methyl-D-aspartate receptor syste m as a major site of ethanol action in the brain and specifically on c ompensatory changes in the expression of the polyamine-sensitive NR2B subunit. Therefore, we examined the effects of chronic ethanol treatme nt on polyamine homeostasis in the rat brain. Wistar rats were made de pendent by ethanol vapor inhalation. This caused a rise in hippocampal ornithine decarboxylase (ODC) activity that was correlated with the a ppearance of physiological dependence. ODC activity returned to contro l levels within 3 days of ethanol withdrawal. Enzyme activity also inc reased in the cerebral cortex, striatum, and cerebellum of the ethanol -dependent rats. The concentration of the polyamines (putrescine, sper midine, and spermine) in the hippocampus was increased in ethanol-depe ndent rats. Injection of the ODC inhibitor, gamma-difluoromethylornith ine (500 mg/kg) at the onset of withdrawal resulted in a significant r eduction in the severity of withdrawal behaviors. The level of ODC act ivity and the severity of withdrawal behaviors were positively correla ted. Perturbed polyamine homeostasis may represent an important molecu lar component in the initiation of ethanol withdrawal behaviors in the ethanol-dependent rat.