Zaprinast impairs spatial memory by increasing PDE5 expression in the rat hippocampus.
Behav Brain Res
; 278: 129-36, 2015 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-25281278
ABSTRACT
In this work, we report the effect of post-training intraperitoneal administration of zaprinast on rat memory retention in the Morris water maze task that revealed a significant memory impairment at the intermediate dose of 10mg/kg. Zaprinast is capable of inhibiting both striatal and hippocampal PDE activity but to a different extent which is probably due to the different PDE isoforms expressed in these areas. To assess the possible involvement of cyclic nucleotides in rat memory impairment, we compared the effects obtained 30 min after the zaprinast injection with respect to 24h after injection by measuring both cyclic nucleotide levels and PDE activity. As expected, 30 min after the zaprinast administration, we observed an increase of cyclic nucleotides, which returned to a basal level within 24h, with the exception of the hippocampal cGMP which was significantly decreased at the dose of 10mg/kg of zaprinast. This increase in the hippocampal region is the result of a cGMP-specific PDE5 induction, confirmed by sildenafil inhibition, in agreement with literature data that demonstrate transcriptional regulation of PDE5 by cAMP/cGMP intracellular levels. Our results highlight the possible rebound effect of PDE inhibitors.
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Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
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Purinonas
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 5
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Hipocampo
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Transtornos da Memória
Limite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Ano de publicação:
2015
Tipo de documento:
Article