Treatment of Acute Alcohol Withdrawal and Long-Lasting Alterations in Hippocampal Neuronal Networks.
L. P. Gonzalez
Univ. of Oklahoma Health Sciences Center, Dept. of Psychiatry & Behavioral Sciences POB 26901, OKC, OK 73190.
Alcoholism: Clinical and Experimental Research, 25(5, Suppl.), 190A. (2003)
Hippocampal function and morphology are sensitive to acute and chronic ethanol exposure and these are altered following alcohol withdrawal. Abnormal electrographic activity is observed within the hippocampus soon after withdrawal and this effect is increased after repeated withdrawal episodes. Benzodiazepines administered during the acute withdrawal syndrome suppress many of the associated symptoms, but only high doses reduce the effects observed in hippocampus and these treatments do not prevent the potentiation of hippocampal withdrawal effects following repeated withdrawals. Measures of hippocampal function also show slowly developing changes in neuronal network interactions long after alcohol withdrawal. For the studies reported here, male rats received 7 to 14 days exposure to ethanol through vapor inhalation. In vivo studies were conducted 21 days after ethanol withdrawal to examine afterdischarge and motor seizures induced by electrical stimulation of the hippocampal CA3 field in freely-moving rats. In vitro hippocampal slices from similarly treated animals were also studied using multielectrode arrays of 64 electrodes to evaluate neuronal network properties. Results from both preparations suggest significant, long-lasting alterations in inhibitory mechanisms modulating hippocampal neuronal excitability and elicited seizure development. Benzodiazepines and glutamate antagonists administered during acute withdrawal failed to prevent these late-onset withdrawal effects, emphasizing the need for further development of additional agents for the treatment of alcohol withdrawal.
Supported in part by NIAAA grants AA09959 & AA12283
