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

A PISERA-FUSTER, J ZWILLER AND R BERNABEU

MOLECULAR NEUROBIOLOGY

HUMANA PRESS INC

Lugar: Totowa, NJ; Año: 2021 vol. 58 p. 2590 - 2607

0893-7648

In zebrafish, nicotine is known to regulate sensitivity to psychostimulants via epigenetic mechanisms. Little however is knownabout the regulation of addictive-like behavior by DNA methylation processes. To evaluate the influence of DNA methylation onnicotine-induced conditioned place preference (CPP), zebrafish were exposed to methyl supplementation through oral Lmethionine(Met) administration. Met was found to reduce dramatically nicotine-induced CPP as well as behaviors associatedwith drug reward. The reduction was associated with the upregulation of DNA methyltransferases (DNMT1 and 3) as well aswith the downregulation of methyl-cytosine dioxygenase-1 (TET1) and of nicotinic receptor subunits. Met also increased theexpression of histone methyltransferases in nicotine-induced CPP groups. It reversed the nicotine-induced reduction in themethylation at α7 and NMDAR1 gene promoters. Treatment with the DNMT inhibitor 5-aza-2′-deoxycytidine (AZA) wasfound to reverse the effects of Met in structures of the reward pathway. Interestingly, Met did not modify the amount of thephospho-form of CREB (pCREB), a key factor establishing nicotine conditioning, whereas AZA increased pCREB levels. Ourdata suggest that nicotine-seeking behavior is partially dependent on DNA methylation occurring probably at specific gene loci,such as α7 andNMDAR1 receptor gene promoters. Overall, they suggest that Met should be considered as a potential therapeuticdrug to treat nicotine addiction.