Methionine Supplementation Abolishes Nicotine-Induced Place Preference in Zebrafish: a Behavioral and Molecular Analysis.

Pisera-Fuster, Antonella; Zwiller, Jean; Bernabeu, Ramon

Pisera-Fuster, Antonella; Zwiller, Jean; Bernabeu, Ramon.

Afiliação

Pisera-Fuster A; Department of Physiology and Institute of Physiology and Biophysics, School of Medicine, University of Buenos Aires, Paraguay 2155 7thfloor (C1121ABG), Ciudad Autónoma de Buenos Aires, Argentina.
Zwiller J; Laboratoire de Neurosciences Cognitives et Adaptatives, Université de Strasbourg, Strasbourg, France.
Bernabeu R; Department of Physiology and Institute of Physiology and Biophysics, School of Medicine, University of Buenos Aires, Paraguay 2155 7thfloor (C1121ABG), Ciudad Autónoma de Buenos Aires, Argentina. rbernabeu@fmed.uba.ar.

Mol Neurobiol ; 58(6): 2590-2607, 2021 Jun.

Article em En | MEDLINE | ID: mdl-33475949

RESUMO

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.

Assuntos

Comportamento Animal/fisiologia; Comportamento de Escolha; Suplementos Nutricionais; Metionina/farmacologia; Nicotina/farmacologia; Peixe-Zebra/fisiologia; 5-Metilcitosina/metabolismo; Animais; Azacitidina/farmacologia; Comportamento Animal/efeitos dos fármacos; Encéfalo/efeitos dos fármacos; Encéfalo/metabolismo; Condicionamento Clássico; Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo; Metilação de DNA/efeitos dos fármacos; Metilação de DNA/genética; Epigênese Genética/efeitos dos fármacos; Fosforilação/efeitos dos fármacos; Subunidades Proteicas/genética; Subunidades Proteicas/metabolismo; RNA Mensageiro/genética; RNA Mensageiro/metabolismo; Receptores de N-Metil-D-Aspartato/genética; Receptores de N-Metil-D-Aspartato/metabolismo; Receptores Nicotínicos/genética; Receptores Nicotínicos/metabolismo; Recompensa; Peixe-Zebra/genética; Proteínas de Peixe-Zebra/genética; Proteínas de Peixe-Zebra/metabolismo

Palavras-chave

Conditioned place preference; DNA methylation; Epigenetics; Nicotine; Zebrafish

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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

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