The neuropeptide galanin coexists with acetylcholine in the septohippocampal pathway, relevant to learning, memory, and Alzheimer's disease. Galanin fibers and terminals are overexpressed in the cholinergic basal forebrain in Alzheimer's disease. Mike McDonald worked out conditions for lesioning cholinergic neurons in the basal forebrain of the rat with the cholinergically selective immunotoxin, 192IgG-saporin, to produce a loss of cholinergic markers and deficits in the delayed non-matching to position memory task in rats, which were analogous to those seen in Alzheimer's dementia. This year, Dr. McDonald completed experiments with galanin, the galanin receptor antagonist, M40, and combinations of cholinergic drugs and galanin compounds, in the cholinergic lesion model. Preliminary data indicate that the combination of M40 with an M1 cholinergic agonist significantly improves performance in the lesioned rats. These findings indicate that galanin overexpression may contribute to the dementia symptoms, and that galanin receptor antagonists may be a useful adjunct therapy to existing cholinergic therapies for treating Alzheimer's dementia.

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