Behavioral Functions of Neuropeptides

Crawley, Jacqueline N.

Abstract

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.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Mental Health (NIMH)
• Type: Intramural Research (Z01)
• Project #: 1Z01MH002177-13
• Application #: 6111124
• Study Section: Special Emphasis Panel (ETB)
• Support Year: 13
• Fiscal Year: 1998

Institution

• Name: U.S. National Institute of Mental Health
• Country: United States

Publications

Crawley, J N (2008) Galanin impairs cognitive abilities in rodents: relevance to Alzheimer's disease. Cell Mol Life Sci 65:1836-41

Bailey, Kathleen R; Pavlova, Maria N; Rohde, Alex D et al. (2007) Galanin receptor subtype 2 (GalR2) null mutant mice display an anxiogenic-like phenotype specific to the elevated plus-maze. Pharmacol Biochem Behav 86:8-20

Crawley, Jacqueline N; Chen, Thomas; Puri, Amit et al. (2007) Social approach behaviors in oxytocin knockout mice: comparison of two independent lines tested in different laboratory environments. Neuropeptides 41:145-63

Wrenn, Craige C; Turchi, Janita N; Schlosser, Sophie et al. (2006) Performance of galanin transgenic mice in the 5-choice serial reaction time attentional task. Pharmacol Biochem Behav 83:428-40

Wiesenfeld-Hallin, Zsuzsanna; Xu, Xiao-Jun; Crawley, Jacqueline N et al. (2005) Galanin and spinal nociceptive mechanisms: recent results from transgenic and knock-out models. Neuropeptides 39:207-10

Karlsson, Rose-Marie; Holmes, Andrew; Heilig, Markus et al. (2005) Anxiolytic-like actions of centrally-administered neuropeptide Y, but not galanin, in C57BL/6J mice. Pharmacol Biochem Behav 80:427-36

He, B; Counts, S E; Perez, S E et al. (2005) Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice. Neuroscience 133:371-80

Rustay, Nathan R; Wrenn, Craige C; Kinney, Jefferson W et al. (2005) Galanin impairs performance on learning and memory tasks: findings from galanin transgenic and GAL-R1 knockout mice. Neuropeptides 39:239-43

Holmes, Andrew; Li, Qian; Koenig, Elizabeth A et al. (2005) Phenotypic assessment of galanin overexpressing and galanin receptor R1 knockout mice in the tail suspension test for depression-related behavior. Psychopharmacology (Berl) 178:276-85

Yoshitake, Takashi; Wang, Fu-Hua; Kuteeva, Eugenia et al. (2004) Enhanced hippocampal noradrenaline and serotonin release in galanin-overexpressing mice after repeated forced swimming test. Proc Natl Acad Sci U S A 101:354-9