GLUTAMATE AND BENZODIAZEPINE RECEPTOR AUTORADIOGRAPHY IN RAT-BRAIN AFTER REPETITION OF ALCOHOL DEPENDENCE

During repeated alcohol withdrawal, convulsive withdrawal behaviour ha s been shown to be increased in a kindling-like manner in both clinica l and experimental studies. In the present experiment, quantitative au toradiography was used to investigate binding of tritiated ligands to glutamate receptor subtypes and the benzodiazepine/GABA (BZ/GABA) rece ptor complex in rats exposed to 14 episodes of alcohol withdrawal, Sei zures were detected in 25% of the animals during withdrawal episode 10 -13. Repeated alcohol withdrawal resulted in a decrease in the number of lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([H-3]-AMPA ) binding sites in striatum and subregions of the entorhinal cortex, t he cerebellum and the hippocampus, while the [H-3]-flunitrazepam bindi ng was down-regulated in the frontal cortex, There was no differences between the controls and the multiple withdrawal animals regarding the [H-3]-dizocilpine ([H-3]-MK801) binding and the [H-3]-kainic acid bin ding. However, within the latter group, those animals in which withdra wal seizures were observed had increased [H-3]-MK801 binding sites in focal regions of entorhinal cortex and hippocampus, compared to those in which seizures were not observed. The decreased AMPA binding sugges ted impaired glutamate neurotransmission, As such, this receptor proba bly did not contribute to alcohol withdrawal kindling, but rather was involved in seizure protective mechanisms during this process.