BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

点击翻译按钮获取中文摘要

The neuropeptide galanin coexists with acetylcholine in the rat septohippocampal pathway, relevant to learning and memory, and is overexpressed in the basal forebrain in Alzheimers disease. We discovered that galanin administration to rats impairs performance on several memory tasks. Last year, postdoctoral fellow Mike McDonald demonstrated that the galanin receptor antagonist, M40, potentiated the beneficial actions of an M-1 muscarinic agonist, TZTP, in rats with 192-IgG saporin cholinergic lesions, on delayed nonmatching to position. These findings support an inhibitory modulatory role for endogenous galanin in modulating cholinergic pathways necessary for memory processes, and indicate that galanin antagonists may be a useful adjunct therapy to existing cholinergic therapies for treating Alzheimers dementia. PUBLICATION: McDonald, Willard, Wenk, Crawley, Coadministration of a galanin antagonist M40 with a muscarinic M1 agonist improved delayed nonmatching to position in rats with choinergic lesions. Journal of Neuroscience 18: 5-78-5085, 1998.Postdoctoral fellow Terri Gleason set up the Morris water task last year, to test the actions of galanin in this widely used memory test. Intraventricularly administered galanin induced performance deficits on latency to find the hidden platform over training trials, and on selective quadrant search during the probe trial. Significant genetic components were detected in responsiveness to galanin. The Wistar and Sprague-Dawley strains were sensitive to the inhibitory actions of galanin, as compared to the Long-Evans strain which was unaffected by galanin treatment in this task. Performance on the visible platform task and in Digiscan exploratory locomotion was normal at doses of galanin which impaired acquisition of the Morris water task. PUBLICATION: Gleason, Dreiling and Crawley, Rat strain differences in response to galanin on the Morris water task. Neuropeptides, in press, 1999.This year our galanin research program received a new research tool. Galanin overexpressing transgenic mice were generated by Robert Steiner and coworkers at the University of Washington, Seattle, and backcrossed for 7 generations into a C57BL/6J background for our behavioral experiments. Postdoctoral fellow Andrew Holmes and several student volunteers conducting the first behavioral phenotyping on galanin transgenic mice and their wild type control littermates. General health, home cage behaviors, neurological reflexes, and motor functions were normal. Impaired performance on several memory tasks was detected in the first pilot studies, primarily in the male transgenics. Experiments employing additional memory tasks, behavioral tests addressing the domains of feeding, analgesia, and anxiety, are now ongoing. - neuropeptides behavior galanin acetylcholine memory Alzheimer's disease