Galantamine improves apomorphine-induced deficits in prepulse inhibition via muscarinic ACh receptors in mice.
Br J Pharmacol
; 156(1): 173-80, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-19133998
ABSTRACT
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. EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apomorfina
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Inibidores da Colinesterase
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Receptores Muscarínicos
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Agonistas de Dopamina
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Galantamina
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Inibição Psicológica
Limite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão