Methionine Supplementation Abolishes Nicotine-Induced Place Preference in Zebrafish: a Behavioral and Molecular Analysis.
Mol Neurobiol
; 58(6): 2590-2607, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-33475949
In zebrafish, nicotine is known to regulate sensitivity to psychostimulants via epigenetic mechanisms. Little however is known about the regulation of addictive-like behavior by DNA methylation processes. To evaluate the influence of DNA methylation on nicotine-induced conditioned place preference (CPP), zebrafish were exposed to methyl supplementation through oral L-methionine (Met) administration. Met was found to reduce dramatically nicotine-induced CPP as well as behaviors associated with drug reward. The reduction was associated with the upregulation of DNA methyltransferases (DNMT1 and 3) as well as with the downregulation of methyl-cytosine dioxygenase-1 (TET1) and of nicotinic receptor subunits. Met also increased the expression of histone methyltransferases in nicotine-induced CPP groups. It reversed the nicotine-induced reduction in the methylation at α7 and NMDAR1 gene promoters. Treatment with the DNMT inhibitor 5-aza-2'-deoxycytidine (AZA) was found to reverse the effects of Met in structures of the reward pathway. Interestingly, Met did not modify the amount of the phospho-form of CREB (pCREB), a key factor establishing nicotine conditioning, whereas AZA increased pCREB levels. Our data suggest that nicotine-seeking behavior is partially dependent on DNA methylation occurring probably at specific gene loci, such as α7 and NMDAR1 receptor gene promoters. Overall, they suggest that Met should be considered as a potential therapeutic drug to treat nicotine addiction.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
/
Peixe-Zebra
/
Comportamento de Escolha
/
Suplementos Nutricionais
/
Metionina
/
Nicotina
Limite:
Animals
Idioma:
En
Revista:
Mol Neurobiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Argentina
País de publicação:
Estados Unidos