Cellular basis of memory for addiction.

Abstract:

:DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. Here, we review the types of molecular and cellular adaptations that occur in specific brain regions to mediate addiction-associated behavioral abnormalities. These include alterations in gene expression achieved in part via epigenetic mechanisms, plasticity in the neurophysiological functioning of neurons and synapses, and associated plasticity in neuronal and synaptic morphology mediated in part by altered neurotrophic factor signaling. Each of these types of drug-induced modifications can be viewed as a form of "cellular or molecular memory." Moreover, it is striking that most addiction-related forms of plasticity are very similar to the types of plasticity that have been associated with more classic forms of "behavioral memory," perhaps reflecting the finite repertoire of adaptive mechanisms available to neurons when faced with environmental challenges. Finally, addiction-related molecular and cellular adaptations involve most of the same brain regions that mediate more classic forms of memory, consistent with the view that abnormal memories are important drivers of addiction syndromes. The goal of these studies which aim to explicate the molecular and cellular basis of drug addiction is to eventually develop biologically based diagnostic tests, as well as more effective treatments for addiction disorders. :Lo central de la drogadicción, a pesar de la importancia de los numerosos factores psicosociales, es que implica un proceso biológico. Un estado de adicción se define por la capacidad que tiene la exposición repetida a una droga de abuso para inducir cambios en un cerebro vulnerable, el impulse a la búsqueda compulsiva y la obtención de drogas, y la pérdida de control sobre el uso de éstas. En este artículo se examinan los tipos de adaptaciones moleculares y celulares que ocurren en regiones especificas del cerebro y que median alteraciones conductuales asociadas con la adicción. Estas adaptaciones incluyen alteraciones en la expresión génica, producidas en parte por mecanismos epigenéticos, en la plasticidad del funcionamiento neurofisiológico de neuronas y sinapsis, y en la plasticidad asociada con la morfología neuronal y sináptica mediada en parte por las señales alteradas del factor neurotrófico, Cada uno de estos tipos de modificaciones inducidos por drogas se puede considerar como una forma de “memoria celular o molecular”. Sin embargo, llama la atención que la mayoría de las formas de plasticidad relacionadas con la adicción son muy similares a los tipos de plasticidad que se han asociado con las formas más clásicas de “memoria conductual”, lo que refleja tal vez el repertorio limitado de los mecanismos de adaptación de que disponen las neuronas cuando se enfrentan con las exigencias del medioambiente. Por último, las adaptaciones moleculares y celulares relacionadas con las adicciones incluyen la mayor parte de las mismas regiones del cerebro que median las formas más clásicas de la memoria, lo que resulta consistente con la opinión de que las memorias anormales son importantes impulsoras de los síndromes adictivos. El propósito de estos estudios que buscan explicar las bases moleculares y celulares de la adicción a drogas es, eventualmente, poder desarrollar pruebas diagnósticas con bases biológicas, como también contar con terapias más efectivas para los trastornos adictivos. :Malgré l'importance de nombreux facteurs psychosociaux, l'addiction à une drogue repose essentiellement sur un processus biologique: l'état de dépendance se définit par la faculté d'une exposition répétée à une consommation de drogue à provoquer des modifications dans un cerveau vulnérable conduisant à leur recherche et à leur prise compulsive et à la perte du contrôle de leur utilisation. Nous analysons ici les types d'adaptation moléculaire et cellulaire qui interviennent dans des régions cérébrales particulières à l'origine des anomalies du comportement addictif: ce sont des altérations de l'expression génique dues en partie à des mécanismes épigénétiques, à la plasticité du fonctionnement neurophysiologique des neurones et des synapses et l'association d'une plasticité au niveau de la morphologie neuronale et synaptique due en partie à une modification de la transmission du signal des facteurs neurotrophiques. Chacun de ces types de modifications induites par les drogues peut être vu comme une forme de «mémoire cellulaire ou moléculaire». De plus, il est frappant de voir que la plupart des formes de plasticité liées à l'addiction sont très semblables aux types de plasticité associés aux formes plus classiques de «mémoire comportementale» reflétant peut-être le caractère limité du répertoire des mécanismes adaptatifs disponibles pour les neurones lorsqu'ils font face aux défis environnementaux. Finalement, les adaptations moléculaires et cellulaires liées à l'addiction concernent la plupart des mêmes régions cérébrales impliquées dans les formes plus classiques de mémoire, ce qui conforte l'idée que des souvenirs anormaux sont d'importants vecteurs de syndromes de dépendance. Le but de ces études, qui expliquent les bases moléculaires et cellulaires de la dépendance à une drogue, est finalement de développer des tests diagnostiques biologiques, ainsi que des traitements plus efficaces pour les troubles addictifs.

authors

Nestler EJ

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

431-43

issue

4

eissn

1294-8322

issn

1958-5969

journal_volume

15

pub_type

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