The role of the Forebrain Cholinergic Projection System in Performance in the Radial-Arm Maze in Memory-Impaired Rats

Summary

After chronic administration of alcohol for 6 months, or ibotenate lesions of the cholinergic projection nuclei to the neocortex and hippocampus, rats showed enduring deficits in 4 different components of memory tested in the radial-arm maze: reference and working spatial and associative memory. Cell suspension transplants of foetal cholinergic-rich (C-R), but not cholinergic-poor (C-P), brain tissue, placed into neocortex and/or hippocampus, substantially reversed deficits in all 4 memory components over a period of 7–13 weeks after grafting. Both alcohol-treated (ALC) and lesioned (LES) animals showed reduced cortical and hippocampal levels of choline acetyltransferase (ChAT) activity. However, in rats with C-R but not C-P transplants, ChAT activity did not differ from control level. Rats were tested before grafting to determine their reaction to acute systemic administration of muscarinic and nicotinic receptor agonists and antagonists. Both ALC and LES animals showed increased sensitivity to the beneficial effects on cognitive performance of cholinergic agonists, and to the deleterious effects of antagonists. Effects of both muscarinic and nicotinic agents were more marked for working than reference memory. Nicotine was particularly effective in improving spatial working memory in LES rats. However, in LES rats tested after grafting with C-R tissue, this compound had the surprising effect of making performance worse, though it continued to reduce errors in animals with sham, or C-P grafts.