Cognition, Behavior, and Memory
Author: Leandro Rocco | Email: lrocco@fmed.uba.ar
Leandro Rocco1°, Joaquín Ortiz1°, María Paula Faillace1°, Ramón Oscar Bernabeu1°
1° IFIBIO Houssay. UBA-CONICET
Epigenetic mechanisms have been studied as an essential cog in the development, maintenance and reinstatement of addiction-related behaviours, whereas its involvement regarding relapse to drugs of abuse have not been fully elucidated. Zebrafish constitutes a practical and verified model used in addiction biology through the conditioned place preference (CPP) task.
In the present study we aimed to evaluate nicotine relapse-related responses and assess the levels of epigenetic markers related to drug reward such as histone acetylation in lysine residues 9 and 27 (H3K9Ac and H3K27Ac) which are associated with chromatin relaxation and higher transcriptional activity. Animals tested on a nicotine-CPP task showed higher levels of H3K9Ac and H3K27Ac in all regions that constitute the reward pathway in comparison to saline-treated controls. Interestingly, in fish that were later subjected to an extinction protocol and evaluated for nicotine relapse, these epigenetic markers remained elevated in brain regions principally with a high number of dopaminergic neurons, such as PTN and Vd/Vv.
In addition to this, using RT-qPCR, we evaluated mRNA levels of key enzymes involved in histone acetylation such as HDAC-1, CBP-A and CBP-B.
These findings suggest that histone acetylation plays a fundamental role in maintaining nicotine induced preference and may regulate susceptibility to relapse, offering a potential target in the treatment of nicotine addiction.