Effects of Nicotine and Histone Deacetylase Inhibitors on the Brain

FAILLACE AND BERNABEU

Neuroscience of Nicotine: Mechanisms and Treatments.

elsevier

Lugar: Londres; Año: 2018;

Exposure to nicotine may produce long-lasting alterations in neuronalplasticity in several brain areas including the mesolimbic reward pathway;howeverlittle is known respect to the molecular mechanisms involved in theseprocesses. Epigenetic modifications are excellent candidates to explore themolecular mechanisms of reward and the consequent nicotine-induced synapticchanges. One of the most studied epigenetic mechanisms is histone acetylation,which can lead to modification in gene expression. This kind of epigeneticchanges can persist for a long time. Histone deacetylases (HDACs) remove acetylgroups from histones thereby facilitating specific gene transcription and theirinhibition has been involved in the enhancement of memory consolidation inrodents. Interestingly, phenylbutyrate (PhB: a HDAC inhibitor) decreases therewarding properties of nicotine in rodents and zebrafish studied as behavioralexperimental models. PhB specifically decreases the rewarding properties ofnicotine without affecting the aversive properties of the drug. Because someHDAC inhibitors are at present tested in clinical trials for cancer we canrealistically hypothesize that these compounds could be used, at appropriatedoses, as a medication to treat nicotine addiction and to help quitting smokingin a near future.