Cognition, Behavior, and Memory
Author: Joaquin Ortiz | Email: joaquinortiz22.jo@gmail.com
Joaquin Ortiz1°, Leandro Rocco1°, Paula Faillace1°, Ramón Oscar Bernabeu1°
1° IFIBIO Houssay (UBA-CONICET)
A goal of addiction research is to gain an understanding of the molecular changes that underlie the onset and persistence of addiction-like behaviors. Drugs of abuse regulate behavioral responses in zebrafish, among others, via epigenetic modifications. We have previously shown that DNA methylation (5mC) is involved in the establishment of a nicotine-induced conditioned place preference (CPP) in zebrafish. However, cytosine hidroxymethylation (5hmC), the first step on DNA demethylation, is a long-lasting epigenetic mechanism not explored yet in the nicotine CPP. To assess the influence of 5hmC on nicotine-CPP we evaluated both 5mC and 5hmC, together with the transcriptional expression of key enzymes of the DNA methylation cycle on structures involved in the zebrafish reward-pathway. Different structures in the reward pathway showed different amounts of positive cells of each marker in experimental groups. Furthermore, the DNA methyltransferases were downregulated, while the mRNA level of TET1 (a DNA demethylase) was increased in the nicotine-CPP group. This suggests that nicotine-rewarding behavior is modulated in part by 5mC but also by 5hmC in a structure dependant manner.
The use of nicotine CPP protocol allowed us to demonstrate that transcriptional expression of enzymes controlling DNA methylation and demethylation were widely modified in the brain reward structures of zebrafish. A deeper analysis is necessary to evaluate if this is a common mechanism for drugs of abuse