Noradrenergic-cholinergic interaction: its possible role in memory dysfunction associated with senile dementia.

Over the past 10 years, cholinergic deficits have been strongly correlated with memory dysfunction. On the other hand the lack of efficacy of direct or indirect cholinergic drugs has led to research in other neurotransmitter systems. Several authors have found miscellaneous results in NE and metabolites levels and in monoamine enzyme activities. These discrepancies have lead to discussions about the homogeneity of the disease. Animal lesion studies point out the importance of the septo-hippocampal cholinergic pathway and the interrelations between ACh and NE in the hippocampal formation. The author performed a series of experiments in rats in which hippocampal ACh activity was reduced (fornix section or destruction of cells in the medial septum) and the NE system modified by clonidine or neurotoxic lesions. The hypothesis was that a lesion of the cholinergic pathway leads to an enhancement of NE activity which inhibits spared ACh neurons. The alpha-2 agonist clonidine would interrupt this loop by decreasing of NE release. Results provide arguments for the author's theory.