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. 2019 Dec;21(4):379-387.
doi: 10.31887/DCNS.2019.21.4/pkenny.

Transcriptional Mechanisms of Drug Addiction

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Free PMC article

Transcriptional Mechanisms of Drug Addiction

Purva Bali et al. Dialogues Clin Neurosci. .
Free PMC article

Abstract

Drugs of abuse can modify gene expression in brain reward and motivation centers, which contribute to the structural and functional remodeling of these circuits that impacts the emergence of a state of addiction. Our understanding of how addictive drugs induce transcriptomic plasticity in addiction-relevant brain regions, particularly in the striatum, has increased dramatically in recent years. Intracellular signaling machineries, transcription factors, chromatin modifications, and regulatory noncoding RNAs have all been implicated in the mechanisms through which addictive drugs act in the brain. Here, we briefly summarize some of the molecular mechanisms through which drugs of abuse can exert their transcriptional effects in the brain region, with an emphasis on the role for microRNAs in this process. .

Las drogas de abuso pueden modificar la expresión génica en los centros cerebrales de recompensa y motivación, lo que contribuye a la remodelación estructural y funcional de estos circuitos favoreciendo la aparición de una adicción. En los últimos años ha habido un importante aumento en la comprensión acerca del modo en que las drogas adictivas inducen la plasticidad transcriptómica en las regiones cerebrales relevantes para la adicción, particularmente en el cuerpo estriado. Las maquinarias de señalización intracelular, los factores de transcripción, las modificaciones de la cromatina y los ARNs reguladores no codificadores se han implicado en los mecanismos a través de los cuales las drogas adictivas actúan en el cerebro. En este artículo se resumen algunos de los mecanismos moleculares a través de los cuales las drogas de abuso pueden ejercer sus efectos transcripcionales en el cerebro, con énfasis en el papel de los microARNs en este proceso.

Les stupéfiants peuvent modifier l’expression génique des centres cérébraux de récompense et de motivation, ce qui participe au remodelage structurel et fonctionnel de ces circuits influant sur l’apparition d’un état d’addiction. Notre compréhension du mécanisme selon lequel les substances addictives induisent une plasticité transcriptomique dans les régions cérébrales correspondant à l’addiction, surtout dans le striatum, a considérablement évolué au cours des dernières années. La signalisation intracellulaire, les facteurs de transcription, les modifications de la chromatine et les ARN de régulation non codants interviennent tous dans les mécanismes d’action des substances addictives sur le cerveau. Nous résumons brièvement ici certains des mécanismes moléculaires qui permettent aux stupéfiants d’exercer leurs effets transcriptionnels sur le cerveau, en insistant sur le rôle des microARN dans ce processus.

Keywords: BDNF; MeCP2; addiction; cocaine; microRNA; striatum; transcription factor.

Figures

Figure 1.
Figure 1.. Interactions between cAMP response element-binding protein (CREB), methyl CpG-binding protein 2 (MeCP2), brain-derived neurotrophic factor (BDNF) and miR-212 in the control of cocaine intake. Cocaine increases the activity or 
expression of CREB, MeCP2, BDNF, and miR-212 in the striatum. In turn, CREB stimulates the expression of dynorphin and other genes that serve to decrease the motivational properties of cocaine and protect against addiction. Conversely, MeCP2 and BDNF increase the motivational properties of cocaine and increase vulnerability to addiction. CREB, MeCP2, and BDNF all share reciprocal interactions with miR-212, with miR-212 modulating the activity or expression to protect against the development of compulsive cocaine use. Red lines indicate an inhibitory action on activity or expression. Green lines indicated a stimulatory action.

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