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Galantamine improves apomorphine‐induced deficits in prepulse inhibition via muscarinic ACh receptors in mice
Author(s) -
Yano K,
Koda K,
Ago Y,
Kobayashi H,
Kawasaki T,
Takuma K,
Matsuda T
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2008.00037.x
Subject(s) - galantamine , apomorphine , muscarinic acetylcholine receptor , pharmacology , chemistry , nicotinic agonist , prepulse inhibition , mecamylamine , oxotremorine , dopamine , acetylcholine , dopamine receptor , agonist , endocrinology , medicine , donepezil , dopaminergic , receptor , biochemistry , dementia , schizophrenia (object oriented programming) , disease , psychiatry
Background and purpose: Galantamine, a weak acetylcholine esterase (AChE) inhibitor and allosteric potentiator of nicotinic ACh receptors (nAChRs), improves apomorphine‐induced deficits in prepulse inhibition (PPI), sensory information‐processing deficits, via a nAChR‐independent mechanism. The present study examined the role of muscarinic ACh receptors (mAChRs) in the effect of galantamine, and studied the mechanism of galantamine‐induced increases in prefrontal ACh levels in mice. Experimental approach: Apomorphine (1 mg kg −1 ) was administered to male ddY mice (9–10 weeks old) to create a PPI deficit model. Extracellular ACh concentrations in the prefrontal cortex were measured by in vivo microdialysis. Key results: Galantamine‐ and donepezil‐mediated improvements in apomorphine‐induced PPI deficits were blocked by the preferential M 1 mAChR antagonist telenzepine. The mAChR agonist oxotremorine also improved apomorphine‐induced PPI deficits. Galantamine, like donepezil, increased extracellular ACh concentrations in the prefrontal cortex. Galantamine‐induced increases in prefrontal ACh levels were partially blocked by the dopamine D 1 receptor antagonist SCH23390, but not by antagonists of mAChRs (telenzepine) and nAChRs (mecamylamine). Galantamine increased dopamine, but not 5‐HT, release in the prefrontal cortex. Conclusions and implications: Galantamine improves apomorphine‐induced PPI deficits by stimulating mAChRs through increasing brain ACh levels via a dopamine D 1 receptor‐dependent mechanism and AChE inhibition.