Sex differences in drug abuse

Becker, Jill B.; Hu, Ming

doi:10.1016/j.yfrne.2007.07.003

Cited by 867 publications

(749 citation statements)

References 131 publications

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“…Substance abuse and addiction have higher prevalence in men than women (Becker & Hu 2008). To explore sex‐effects, we tested for an interaction between sex and PRS and found significant interactions ( P < 0.05) for SCZ‐PRS in alcohol and cocaine use disorders.…”

Section: Resultsmentioning

confidence: 99%

Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

et al. 2017

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We use polygenic risk scores (PRSs) for schizophrenia (SCZ) and bipolar disorder (BPD) to predict smoking, and addiction to nicotine, alcohol or drugs in individuals not diagnosed with psychotic disorders. Using PRSs for 144 609 subjects, including 10 036 individuals admitted for in‐patient addiction treatment and 35 754 smokers, we find that diagnoses of various substance use disorders and smoking associate strongly with PRSs for SCZ (P = 5.3 × 10−50–1.4 × 10−6) and BPD (P = 1.7 × 10−9–1.9 × 10−3), showing shared genetic etiology between psychosis and addiction. Using standardized scores for SCZ and BPD scaled to a unit increase doubling the risk of the corresponding disorder, the odds ratios for alcohol and substance use disorders range from 1.19 to 1.31 for the SCZ‐PRS, and from 1.07 to 1.29 for the BPD‐PRS. Furthermore, we show that as regular smoking becomes more stigmatized and less prevalent, these biological risk factors gain importance as determinants of the behavior.

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Section: Resultsmentioning

confidence: 99%

Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

et al. 2017

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“…22 Furthermore, previous work has hypothesized that estradiol receptors (Esr2) are anatomically positioned in the striatum to promote dopamine release produced by administration of drugs of abuse, such as cocaine. 23,24 Thus, the present study also compared changes in Esr2 gene expression in the NAcc across our experimental conditions.…”

Section: Original Investigationmentioning

confidence: 99%

Nicotine Withdrawal Increases Stress-Associated Genes in the Nucleus Accumbens of Female Rats in a Hormone-Dependent Manner

Torres

Pipkin

Ferree

et al. 2015

Nicotine & Tobacco Research

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IntroductionTobacco use is the number one cause of preventable deaths in the United States. 1 Of particular concern is the high rate of tobacco use among women, who are more susceptible to the negative health consequences of long-term smoking than men. 2 As a result, tobacco use is believed to be a major contributing factor to health disparities in women. In spite of the magnitude of the problem, surprisingly little is known about the underlying biological factors that promote tobacco relapse in females.Much work has suggested that stress promotes tobacco use in women. For example, women report more negative mood states, such as depression, anxiety, and intense craving during smoking abstinence than men. [3][4][5] Women also use more tobacco products and display lower quit rates relative to men. 6 Furthermore, women report that they maintain tobacco use to relieve intense withdrawal symptoms that emerge during abstinence, and they claim more often than men that the anxiety-reducing effects of cigarettes are the main reason for smoking. [7][8][9] Preclinical studies have shown that the behavioral and biological consequences of nicotine withdrawal are greater in female versus AbstractIntroduction: Previous work led to our hypothesis that sex differences produced by nicotine withdrawal are modulated by stress and dopamine systems in the nucleus accumbens (NAcc). We investigated our hypothesis by studying intact females to determine whether the mechanisms that promote withdrawal are ovarian-hormone mediated. Methods: Female rats were ovariectomized (OVX) or received sham surgery (intact) on postnatal day (PND 45-46). On PND 60, they received sham surgery (controls) or were prepared with nicotine pumps. Fourteen days later, half of the rats had their pumps removed (nicotine withdrawal) and the other half received sham surgery (nicotine exposure). Twenty-four hours later, the rats were tested for anxiety-like behavior using the elevated plus maze and light/dark transfer procedures. The NAcc was then dissected for analysis of several genes related to stress (CRF, UCN, CRF-R1, CRF-R2, CRF-BP, and Arrb2) or receptors for dopamine (Drd1 and Drd2) and estradiol (Esr2). Results: During withdrawal, intact females displayed an increase in anxiety-like behavior in both tests and CRF, UCN, and Drd1 gene expression. During nicotine exposure, intact females displayed a decrease in CRF-R1, CRF-R2, Drd3, and Esr2 gene expression and an increase in CRF-BP. This pattern of results was absent in OVX females. Conclusions: Nicotine withdrawal produced an increase in anxiety-like behavior and stress-associated genes in intact females that is distinct from changes produced by nicotine exposure. The latter effects were absent in OVX females, suggesting that stress produced by withdrawal is ovarianhormone mediated. These findings have important implications towards understanding tobacco use liability among females.

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“…For example, female rats will work harder for cocaine during estrus than during other phases of the estrous cycle (Roberts et al, 1989;Carroll et al, 2002) and E treatment given to ovariectomized (OVX) rats enhances the motivation to self-administer cocaine (Becker et al, 2007). When various doses of cocaine are available, female rats choose higher doses of cocaine during estrus than during other phases of the estrous cycle (Lynch et al, 2000).…”

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confidence: 99%

Acquisition of cocaine self-administration in ovariectomized female rats: Effect of estradiol dose or chronic estradiol administration

Becker

2008

Drug and Alcohol Dependence

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This study was conducted to investigate whether the dose of estradiol (E) administered acutely, or chronic delivery of one dose of E impacts acquisition and subsequent cocaine self-administration in ovariectomized (OVX) female rats. Five groups of female rats were compared: OVX females treated with 0, 1, 2, or 5 µg 17 β-E, 30 min prior to the self-administration session, and OVX rats that received a 1.5 mg E pellet (designed to chronically release 25 µg E/d X 60 d) implanted 1 week before cocaine self-administration initiation. Rats were tested in 1 hr sessions on a FR1 schedule with the dose of cocaine increasing every week (testing occurred 5 day/wk; doses: 0.2, 0.3, 0.4, 0.5 and 0.75 mg/kg/ infusion). We report that OVX rats treated with 2 µg E acquired self-administration more rapidly than all of the other groups, and animals that received 1 or 2 µg E self-administered significantly more cocaine compared to OVX+vehicle at 0.3 and 0.4 mg/kg/infusion. In contrast, OVX rats given 5 µg E acutely, or chronic E via slow-release pellets did not take more cocaine than the OVX+vehicle group at any time point. Physiological serum concentrations of E were seen with 1 or 2 µg E, but 5 µg E and the E pellet produced supra-physiological concentrations. These results suggest an inverted U-shaped dose-response curve for the effect of E on acquisition of cocaine self-administration.

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Sex differences in drug abuse

Cited by 867 publications

References 131 publications

Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

Nicotine Withdrawal Increases Stress-Associated Genes in the Nucleus Accumbens of Female Rats in a Hormone-Dependent Manner

Acquisition of cocaine self-administration in ovariectomized female rats: Effect of estradiol dose or chronic estradiol administration

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