IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
artículos
Título:
Pre-Exposure to Nicotine with Nocturnal Abstinence Induces Epigenetic Changes that Potentiate Nicotine Preference
Autor/es:
FAILLACE, MARIA PAULA; PISERA-FUSTER, ANTONELLA; BERNABEU, RAMON
Revista:
MOLECULAR NEUROBIOLOGY
Editorial:
HUMANA PRESS INC
Referencias:
Año: 2019 vol. 57 p. 1828 - 1846
ISSN:
0893-7648
Resumen:
Prior exposure to drugs of abuse may facilitate addiction. It has been described that pre-exposure to nicotine can increase or,contrarily, prevent conditioned place preference (CPP). Here, we evaluated the effect of nicotine pre-exposure on CPP performanceusing an original protocol mimicking smokers? behaviour in zebrafish.We simulated nicotine withdrawal at sleep time byexposing zebrafish to nicotine during daylight but not at night (D/N) for 14 days and then performed nicotine-CPP in zebrafish.D/N-nicotine-treated zebrafish obtained the highest CPP score, whereas zebrafish pre-exposed continuously to nicotine did notshow nicotine-CPP. Evaluation of locomotor activity, seeking and anxiety-like behaviours supported the CPP findings. Nicotinicreceptor subunit gene expression showed significant increases in the brain of zebrafish exposed to nicotine. Zebrafish exposed toD/N-nicotine showed further increases of α6- and α7-subunit expression after CPP establishment. Inhibition of histone acetylationby phenylbutyrate prevented nicotine-CPP. Transcriptional expression of epigenetic enzymes controlling histoneacetylation/deacetylation and DNA methylation/demethylation was widely modified in brain portions containing reward areasof zebrafish exposed to D/N-nicotine after CPP. Zebrafish exposed to D/N-nicotine showed high levels of acetylated histone 3and pCREB immunoreactivity differentially found in nuclei of the dopaminergic reward circuit in zebrafish homologous to theventral tegmental area, nucleus accumbens and dorsal habenula. Our findings demonstrated that repetitive abstinent periods arerisky factors for drug abuse that potentiate nicotine?environment associations and seeking. Brain modifications can persist longafter nicotine use and are likely due to changes in the transcriptional expression of enzymes regulating drug reward-related geneexpression via epigenetic modifications.