Alcohol withdrawal in mice: Electroencephalographic and behavioral correlates

Abstract

Chronic bipolar electrodes were implanted in forebrain structures of mice including dorsal hippocampus, dorsal-frontal cortex, dorsal-lateral thalamus and septum. Two weeks after surgery, the mice were reduced to 85–90% of free-feeding weight, and physical dependence on alcohol was established by maintaining the mice on an alcohol-containing liquid diet for 6 days. A control group was pair-fed an identical liquid diet except sucrose was substituted isocalorically for alcohol. Following 6 days of consumption alcohol was withdrawn and the development of both EEG and behavioral sequelae of withdrawal was monitored for 6–8h. Only mice withdrawn from alcohol exhibited behavioral signs of withdrawal which included hyperactivity, severe tremor, ataxia, sudden sprawling movements, and clonic-tonic convulsions. No abnormal behavior and no abnormal EEG activity resulted from the withdrawal of the sucrose control diet. EEG recordings during withdrawal from alcohol, however, indicated a progressive development of widespread neural epileptiform activity beginning with EEG slowing and increased amplitudes, followed by single spike events and often leading to sustained epileptic seizure discharge. Similar abnormal EEG patterns were observed throughout the forebrain including cortex, thalamus, hippocampus and septal area. The development of abnormal EEG activity was more severe during the second alcohol withdrawal period following 4 days of alcohol exposure than during the first alcohol withdrawal period following 6 days of alcohol exposure. It is hypothesized that the widespread forebrain epileptiform activity originates in, or is organized from, a central pacemaking region such as midline thalamus or reticular formation.