Functional interactions of galanin and acetylcholine: relevance to memory and Alzheimer's disease.

Galanin, a 29-amino acid neuropeptide, is the only peptide known to coexist with acetylcholine in the basal forebrain neurons which degenerate early in the progression of Alzheimer's disease. Biochemical and neurophysiological studies demonstrated inhibitory actions of galanin on cholinergic functions. Behavioral investigations found that intracerebrally administered galanin produces deficits on spatial learning and memory tasks in rats. Taken together, the current literature suggests that galanin acts as an inhibitory modulator of acetylcholine in this coexistence. Particularly in the case of Alzheimer's disease, where cholinergic activity is severely compromised, the negative actions of galanin may be particularly deleterious. Recently developed galanin antagonists may provide a novel therapeutic approach toward enhancing memory processes in Alzheimer's disease, by removing the putative inhibitory actions of endogenous galanin on the remaining basal forebrain cholinergic neurons.