Administration of Donepezil Does Not Rescue Galanin-Induced Spatial Learning Deficits

ABSTRACT The neuropeptide galanin inhibits the evoked release of several neurotransmitters including acetylcholine and modulates adenylate cyclase (AC) activity. Galanin has also been established to impair various forms of learning and memory in rodents. However, whether galanin produces learning deficits by inhibiting cholinergic activity or decreasing AC function has not been clearly established. The current study investigated if donepezil, an acetylcholinesterase inhibitor utilized in Alzheimer's disease, could rescue galanin-induced Morris water task deficits in rats. The results demonstrated that donepezil did not alter the previously established deficits induced by galanin. These findings suggest that galanin-mediated spatial learning deficits may be unrelated to its modulation of the cholinergic system.

[1]  J. Hohmann,et al.  Galanin transgenic mice display cognitive and neurochemical deficits characteristic of Alzheimer's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  E. Mufson,et al.  A Confocal Microscopic Analysis of Galaninergic Hyperinnervation of Cholinergic Basal Forebrain Neurons in Alzheimer's Disease , 1997, Brain pathology.

[3]  G. Dawson,et al.  The effects of novel cholinesterase inhibitors and selective muscarinic receptor agonists in tests of reference and working memory , 1993, Behavioural Brain Research.

[4]  E. Wei,et al.  Reversal of scopolamine-induced spatial memory deficits in rats by TAK-147. , 2002, Acta pharmacologica Sinica.

[5]  K. Tokita,et al.  Combination of a novel antidementia drug FK960 with donepezil synergistically improves memory deficits in rats , 2002, Pharmacology Biochemistry and Behavior.

[6]  J. Crawley,et al.  Galanin impairs performance on learning and memory tasks: Findings from galanin transgenic and GAL-R1 knockout mice , 2005, Neuropeptides.

[7]  A. Pramanik,et al.  Effects of ventral hippocampal galanin on spatial learning and on in vivo acetylcholine release in the rat , 1996, Neuroscience.

[8]  S. Grillner,et al.  Galanin induces a hyperpolarization of norepinephrine-containing locus coeruleus neurons in the brainstem slice , 1995, Neuroscience.

[9]  P. Deyn,et al.  Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model , 2005, Psychopharmacology.

[10]  G. Kinney,et al.  Galanin Receptor-Mediated Inhibition of Glutamate Release in the Arcuate Nucleus of the Hypothalamus , 1998, The Journal of Neuroscience.

[11]  J. Crawley,et al.  Central galanin administration blocks consolidation of spatial learning , 2003, Neurobiology of Learning and Memory.

[12]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[13]  Ü. Langel,et al.  Galaninergic signalling and adenylate cyclase , 1998, Neuropeptides.

[14]  J. Kehr,et al.  Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Crawley,et al.  Deficits in trace cued fear conditioning in galanin-treated rats and galanin-overexpressing transgenic mice. , 2002, Learning & memory.

[16]  R. Doody,et al.  Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: final analysis of a US multicentre open-label study , 2000, European Neuropsychopharmacology.

[17]  S. Henriksen,et al.  Impairment of memory consolidation by galanin correlates with in vivo inhibition of both LTP and CREB phosphorylation , 2009, Neurobiology of Learning and Memory.

[18]  M. Beal,et al.  Galanin immunoreactivity is increased in the nucleus basalis of meynert in Alzheimer's disease , 1990, Annals of neurology.

[19]  P. D. De Deyn,et al.  Cognitive evaluation of disease-modifying efficacy of donepezil in the APP23 mouse model for Alzheimer’s disease , 2008, Psychopharmacology.

[20]  G. Fisone,et al.  Galanin Reduces Carbachol Stimulation of Phosphoinositide Turnover in Rat Ventral Hippocampus by Lowering Ca2+ Influx Through Voltage‐Sensitive Ca2+ Channels , 1991, Journal of neurochemistry.

[21]  D. Treit,et al.  Thigmotaxis as a test for anxiolytic activity in rats , 1988, Pharmacology Biochemistry and Behavior.

[22]  Yongxiang Zhang,et al.  Bright lighting conditions during testing increase thigmotaxis and impair water maze performance in BALB/c mice , 2012, Behavioural Brain Research.

[23]  N. Birnberg,et al.  A cyclic AMP- and phorbol ester-inducible DNA element , 1986, Nature.

[24]  J. Kehr,et al.  Intraseptal muscarinic ligands and galanin: influence on hippocampal acetylcholine and cognition , 2004, Neuroscience.

[25]  Eric R. Kandel,et al.  Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation , 1990, Nature.

[26]  T. Hökfelt,et al.  Galanin inhibits acetylcholine release in the ventral hippocampus of the rat: histochemical, autoradiographic, in vivo, and in vitro studies. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[27]  J. Kehr,et al.  Galanin and learning , 1999, Brain Research.

[28]  J. Csernansky,et al.  Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse model of Alzheimer’s disease , 2005, Psychopharmacology.

[29]  S. Grillner,et al.  Galanin–5-hydroxytryptamine interactions: electrophysiological, immunohistochemical and in situ hybridization studies on rat dorsal raphe neurons with a note on galanin R1 and R2 receptors , 1998, Neuroscience.

[30]  V. Chan‐Palay Galanin hyperinnervates surviving neurons of the human basal nucleus of meynert in dementias of alzheimer's and parkinson's disease: A hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia , 1988, The Journal of comparative neurology.

[31]  J. Crawley,et al.  Intraseptal galanin potentiates scopolamine impairment of delayed nonmatching to sample , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  E. Mufson,et al.  Galanin fiber hyperinnervation preserves neuroprotective gene expression in cholinergic basal forebrain neurons in Alzheimer's disease. , 2009, Journal of Alzheimer's disease : JAD.