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Review
. 2016 Dec;18(4):395-402.
doi: 10.31887/DCNS.2016.18.4/jbecker.

Sex differences in addiction

Jill B Becker  1
Affiliations
Review

Sex differences in addiction

Jill B Becker. Dialogues Clin Neurosci. 2016 Dec.

Abstract
in English, Spanish, French

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.

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.

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.

Keywords: addiction; amphetamine; cocaine; drug abuse; sex difference; substance use.

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Figures

Figure 1.
Figure 1.. Figure 1. Females are more likely to develop a preference for cocaine. (A) The development of cocaine preferences in male (open circles) and female (filled circles) rats (n =12 per sex). Significant increase in the proportion of cocaine-preferring (CP) females between the second and last fixed-ratio 5 (FR5) tests (*P=0.05). The proportion of CP females was greater than males ($P=0.05). (B) The stability of preferences in pellet-preferring (PP) rats and CP rats (both before and after CP developed). Significant difference between PP and CP rats within same preference category (#P=0.05). Significant difference in preference category before and after CP developed (*P=0.05). Significant difference between the “preference for cocaine” and “preference for pellets” categories within a given group (^P=0.05). PP rats (n = 16) and CP rats (n = 8). (C) Representative self-administration behavior in a PP rat over the 21 FR sessions, displaying the number of infusions (gray) and pellets (black) earned each day during the cocaine-only or pellet-only sessions (closed symbols) and the choice session (open symbols). (D) Representative self-administration behavior in a CP rat (CP criteria met on day 11 in this case). Reproduced from ref 44: Perry AN, Westenbroek C, Becker JB. The development of a preference for cocaine over food identifies individual rats with addiction-like behaviors. PLoS ONE. 2013;8(11):e79465. Reproduced under the Creative Commons Attribution License.
Figure 2.
Figure 2.. A sagittal section of the rat brain depicting some of the neural systems involved in the reward system. Not shown are the glutamate projections from frontal cortex and other brain regions, as well as the GABAergic neurons and the enkaphalin and dynorphin neurons in the nucleus accumbens and dorsal striatum. BST, bed nucleus of the stria terminalis; CeA, central nucleus of the amygdala; DS, dorsal striatum; Fcx, frontal cortex; LC, locus coeruleus; NAc, nucleus accumbens; NTS, nucleus tractus solitarus; VTA/SN, ventral tegmental area/substantia nigra. Reproduced from ref 8: Becker JB, Perry AN, Westenbroek C. Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis. Biol Sex Differ. 2012;3(1):14. Reproduced under the Creative Commons Attribution License. Copyright © 2012, Becker et al, licensee BioMed Central Ltd.
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