INCREASED NMDA-INDUCED EXCITABILITY DURING ETHANOL WITHDRAWAL - A BEHAVIORAL AND HISTOLOGICAL STUDY

Intrahippocampal injections of N-methyl-D-aspartic acid (NMDA) leads t o neurodegeneration in a dose-dependent manner. Chronic administration of ethanol to animals leads to CNS tolerance and dependence. Hyperexc itability following ethanol withdrawal is thought to be related to inc reased sensitivity of the NMDA receptors. The purpose of this study wa s to investigate this predisposition to hyperexcitability by intrahipp ocampal injection of low doses of NMDA. Using control and ethanol-with drawn male Wistar rats, behavioural indices were determined immediatel y after injection and morphological damage was assessed after a period of recovery. There was significantly increased hyperactivity in the e thanol-treated rats immediately after injection. Morphological damage resulting from 5 nmol of NMDA was significantly greater in the CA3 reg ion of the hippocampus in these animals. These data support the hypoth esis that ethanol dependence and subsequent withdrawal is associated w ith increased sensitivity to NMDA which may underlie ethanol withdrawa l-associated brain damage.