The muscarinic acetylcholine receptor is linked via hydrolysis of phosphoinositides to the protein kinase C pathway. In a preceding paper (Beldhuis, H. J. A., H. G. J. Everts, E. A. Vander Zee, P. G. M. Luiten, and B. Bohus (1992) Amygdala kindling-induced seizures selectively impair spatial memory. 1. Behavioral characteristics and effects on hippocampal neuronal protein kinase C isoforms. Hippocampus 2:397-410), the role of different isoforms of protein kinase C in neurobiological processes associated with plasticity was studied using both a spatial learning paradigm and amygdala kindling in the rat. This study extended the findings on protein kinase C activity to the level of the muscarinic acetylcholine receptor. Rats were trained in a spatial learning paradigm and kindled simultaneously in the amygdala to develop generalized motor convulsions. Control rats were trained only in the spatial learning paradigm to acquire stable working and reference memory performance. Alteration in the expression of the muscarinic acetylcholine receptor was investigated using a monoclonal antibody to muscarinic acetylcholine receptor proteins. Trained control rats that were exposed repeatedly to the spatial learning paradigm showed an increase in immunoreactivity for the muscarinic acetylcholine receptor located in the same hippocampal regions in which the protein kinase C activity was increased. In fully kindled rats, however, this increase located in principal neurons was absent, whereas expression of muscarinic acetylcholine receptor proteins was increased in hippocampal astrocytes. Moreover, fully kindled rats showed an impairment in reference memory performance as compared to trained control rats.(ABSTRACT TRUNCATED AT 250 WORDS)