IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
artículos
Título:
Histone deacetylase inhibition decreases preference without affecting aversion for nicotine
Autor/es:
PASTOR VERONICA; HOST LIONEL; ZWILLER JEAN; BERNABEU RAMON OSCAR
Revista:
JOURNAL OF NEUROCHEMISTRY
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2011 vol. 116 p. 636 - 645
ISSN:
0022-3042
Resumen:
Epigenetic mechanisms have recently been shown to be involved in the
long-term effects of drugs of abuse. A well described epigenetic
mechanism modulating transcriptional activity consists in the binding
to DNA of methyl-CpG binding proteins, such as MeCP2, recruiting
histone deacetylases (HDACs). Nicotine causes long-term changes in the
brain, but little is known concerning the mechanisms involved in
nicotine-preference. Using a nicotine-conditioned place preference
protocol, we demonstrate here that the histone deacetylase inhibitor
phenylbutyrate was able to dramatically reduce the preference for
nicotine, without altering the aversive properties of the drug. We
measured immunohistochemically the acetylation of lysine-9 of histone
H3, and the expression of phosphorylated cAMP-response element-binding
protein, HDAC2 and methyl-CpG-binding protein 2 in the striatum and
prefrontal cortex of rats displaying nicotine-preference or aversion
and treated with phenylbutyrate. We show that, at the dose
administered, the inhibitor was effective in inhibiting HDAC activity.
The data suggest that phosphorylated cAMP-response element-binding
protein participates in the establishment of conditioned place
preference, but not in the reduction of nicotine-preference in response
to phenylbutyrate. Moreover, striatal expression of HDAC2 in response
to phenylbutyrate mirrored the behavioral effects of the inhibitor,
suggesting that HDAC2 is involved in promoting synaptic plasticity
underlying the preference for nicotine.