Improved radial maze performance induced by the benzodiazepine antagonist ZK 93 426 in lesioned and alcohol-treated rats

Effects of the benzodiazepine receptor antagonist ZK 93 426 were examined in two groups of rats with long lasting radial maze impairments caused by either ibotenic acid lesions to cholinergic forebrain projections or 28 weeks of alcohol treatment. Animals were trained on the 8-arm radial maze prior to ibotenic acid treatment or following chronic alcohol treatment. Spatial and associative working and reference memory were investigated in parallel. Lesioned rats showed high error rates in all aspects of memory, but particularly in spatial working memory, whilst error rates in alcohol-treated rats were low and uniform. ZK 93 426 improved performance in both experiments. In lesioned rats working memory errors were selectively decreased, in line with evidence that ZK 93 426 enhances attention. However in alcohol-treated rats both reference and working memory errors were reduced to control level, suggesting that these animals primarily showed a mild attentional deficit. Alcohol treatment and lesions were both found to reduce cortical choline acetyltransferase activity, but in view of the non-specificity of alcohol or ibotenic acid to cholinergic neurons and the wide distribution of the GABA-BZ receptor complex, interactions of ZK 93 426 with other systems cannot be ruled out.