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      Sex differences in addiction Translated title: Diferencias por sexo en las adicciones Translated title: Les différences selon le sexe dans l'addiction

      research-article
      , PhD *
      Dialogues in Clinical Neuroscience
      Les Laboratoires Servier
      addiction, amphetamine, cocaine, drug abuse, sex difference, substance use

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          Abstract

          Women exhibit more rapid escalation from casual drug taking to addiction, exhibit a greater withdrawal response with abstinence, and tend to exhibit greater vulnerability than men in terms of treatment outcome. In rodents, short-term estradiol intake in female rats enhances acquisition and escalation of drug taking, motivation for drugs of abuse, and relapse-like behaviors. There is also a sex difference in the dopamine response in the nucleus accumbens. Ovariectomized female rats exhibit a smaller initial dopamine increase after cocaine treatment than castrated males. Estradiol treatment of ovariectomized female rats enhances stimulated dopamine release in the dorsolateral striatum, but not in the nucleus accumbens, resulting in a sex difference in the balance between these two dopaminergic projections. In the situation where drug-taking behavior becomes habitual, dopamine release has been reported to be enhanced in the dorsolateral striatum and attenuated in the nucleus accumbens. The sex difference in the balance between these neural systems is proposed to underlie sex differences in addiction.

          Translated abstract

          Las mujeres presentan una escalada más rápida desde una ingesta casual de una droga hasta la adicción, una mayor respuesta de privación con la abstinencia, y tienden a presentar una mayor vulnerabilidad que los hombres respecto a los resultados del tratamiento. En roedores, el consumo de estradiol a corto plazo en ratas hembra refuerza la adquisición y escalada de la ingesta de drogas, la motivación por las drogas de abuso y las conductas tipo recaída. También hay una diferencia por sexo en la respuesta de dopamina en el núcleo accumbens. Las ratas ovariectomizadas presentan un menor incremento inicial de dopamina después del tratamiento con cocaína respecto a los machos castrados. El tratamiento con estradiol de las ratas ovariectomizadas aumenta la liberación de dopamina por estimulación del estriado dorsolateral, pero no del núcleo accumbens, lo que determina una diferencia por sexo en el balance entre estas dos vías dopaminérgicas. En situaciones en que la conducta de ingestión de la droga se hace habitual, se ha encontrado que la liberación de dopamina está aumentada en el estriado dorsolateral y atenuada en el núcleo accumbens. Se ha propuesto que la diferencia por sexo en el balance entre estos sistemas neurales está a la base de las diferencias por sexo en las adicciones.

          Translated abstract

          Les femmes passent plus rapidement de la consommation occasionnelle de drogue à l'addiction, souffrent d'un syndrome de sevrage plus sévère et sont plus vulnérables que les hommes en termes de résultat thérapeutique. Chez les rongeurs, la prise d'estradiol à court terme chez les rates augmente la propension pour la drogue et l'escalade de sa prise, la motivation pour les drogues illicites et les tendances à la rechute. Il y a aussi une différence selon le sexe dans la réponse à la dopamine dans le noyau accumbens. Des rates ovariectomisées présentent une plus faible augmentation de la dopamine initiale après traitement par cocaïne que des mâles castrés. Le traitement par estradiol de rates ovariectomisées favorise la libération de dopamine dans le striatum dorsolatéral, mais pas dans le noyau accumbens, conduisant à une différence selon le sexe dans l'équilibre entre les deux projections dopaminergiques. Dans les situations de prises de drogue habituelles, la libération de dopamine est augmentée dans le striatum dorsolatéral et atténuée dans le noyau accumbens. La différence selon le sexe dans l'équilibre entre ces systèmes neuronaux sous-tendrait les différences selon le sexe dans l'addiction.

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          Most cited references78

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          Modulation of striatal projection systems by dopamine.

          The basal ganglia are a chain of subcortical nuclei that facilitate action selection. Two striatal projection systems--so-called direct and indirect pathways--form the functional backbone of the basal ganglia circuit. Twenty years ago, investigators proposed that the striatum's ability to use dopamine (DA) rise and fall to control action selection was due to the segregation of D(1) and D(2) DA receptors in direct- and indirect-pathway spiny projection neurons. Although this hypothesis sparked a debate, the evidence that has accumulated since then clearly supports this model. Recent advances in the means of marking neural circuits with optical or molecular reporters have revealed a clear-cut dichotomy between these two cell types at the molecular, anatomical, and physiological levels. The contrast provided by these studies has provided new insights into how the striatum responds to fluctuations in DA signaling and how diseases that alter this signaling change striatal function.
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            D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons.

            Dopamine shapes a wide variety of psychomotor functions. This is mainly accomplished by modulating cortical and thalamic glutamatergic signals impinging upon principal medium spiny neurons (MSNs) of the striatum. Several lines of evidence suggest that dopamine D1 receptor signaling enhances dendritic excitability and glutamatergic signaling in striatonigral MSNs, whereas D2 receptor signaling exerts the opposite effect in striatopallidal MSNs. The functional antagonism between these two major striatal dopamine receptors extends to the regulation of synaptic plasticity. Recent studies, using transgenic mice in which cells express D1 and D2 receptors, have uncovered unappreciated differences between MSNs that shape glutamatergic signaling and the influence of DA on synaptic plasticity. These studies have also shown that long-term alterations in dopamine signaling produce profound and cell-type-specific reshaping of corticostriatal connectivity and function.
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              • Article: not found

              High impulsivity predicts the switch to compulsive cocaine-taking.

              Both impulsivity and novelty-seeking have been suggested to be behavioral markers of the propensity to take addictive drugs. However, their relevance for the vulnerability to compulsively seek and take drugs, which is a hallmark feature of addiction, is unknown. We report here that, whereas high reactivity to novelty predicts the propensity to initiate cocaine self-administration, high impulsivity predicts the development of addiction-like behavior in rats, including persistent or compulsive drug-taking in the face of aversive outcomes. This study shows experimental evidence that a shift from impulsivity to compulsivity occurs during the development of addictive behavior, which provides insights into the genesis and neural mechanisms of drug addiction.
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                Author and article information

                Contributors
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                December 2016
                December 2016
                : 18
                : 4
                : 395-402
                Affiliations
                Department of Psychology, Molecular and Behavioral Neuroscience Institute, University of Michigan
                Author notes
                [* ] E-mail:
                Article
                10.31887/DCNS.2016.18.4/jbecker
                5286725
                28179811
                9ab277f6-6797-4ae1-842c-1a65606fa557
                Copyright: © 2016 Institut la Conference Hippocrate - Servier Research Group

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Translational Research

                Neurosciences
                addiction,amphetamine,cocaine,drug abuse,sex difference,substance use
                Neurosciences
                addiction, amphetamine, cocaine, drug abuse, sex difference, substance use

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