Galanin is a neuropeptide that play an important role in memory formation and may contribute to the cognitive deficits in Alzheimer's disease. Therefore, galanin receptor antagonists may be for drugs for treating memory loss in Alzheimer's disease. The goal of the proposed studies is to determine whether a novel non-peptide galanin receptor ligand, galnon, exhibits similar disruptive effects on memory in rats as galanin. In the initial experiments, galnon will be administered into the lateral ventricle and into the ventral hippocampus to establish a dose- response relationship and to determine the extent that the effects of galnon can be localized to the ventral hippocampus (Aim 1). Next, galanin antagonists will be co-administered with galnon into these sites to confirm that the performance disruption of the memory tasks is mediated by galanin receptors (Aim 2). Finally, the potential for galnon to cross the blood-brain barrier and produce effects on memory will be assessed by administering it systemically (Aim 3). Successful demonstration of mnemonic effects of galnon similar to those of galanin will lead to a comprehensive program to modify galnon's chemical structure to produce a galanin antagonist that crosses the blood-brain barrier, is stable in vivo, and that posses memory-enhancing properties.
NIH ExPorter
NIH ExPorter