Sex/Gender Differences in the Time-Course for the Development of Substance Use Disorder: A Focus on the Telescoping Effect

Pharmacological Reviews, Год журнала: 2022, Номер 75(2), С. 217 - 249

Опубликована: Дек. 12, 2022

Sex/gender effects have been demonstrated for multiple aspects of addiction, with one the most commonly cited examples being "telescoping effect" where women meet criteria and/or seek treatment substance use disorder (SUD) after fewer years drug as compared men. This phenomenon has reported classes including opioids, psychostimulants, alcohol, and cannabis, well nonpharmacological addictions, such gambling. However, there are some inconsistent reports that show either no difference between men or opposite a faster course to addiction in than women. Thus, goals this review evaluate evidence against telescoping effect determine conditions/populations which is relevant. We also discuss from preclinical studies, strongly support validity female animals develop addiction-like features (e.g., compulsive use, an enhanced motivation drug, drug-craving/vulnerability relapse) more readily male animals. biologic factors may contribute effect, ovarian hormones, its neurobiological basis focusing on mesolimbic dopamine reward pathway corticomesolimbic glutamatergic considering critical roles these pathways play rewarding/reinforcing addictive drugs SUD. conclude future research directions, intervention strategies prevent development SUD

Significance Statement

One widely gender/sex differences effect," reflects accelerated versus seeking evaluates drawing upon data both clinical studies. contribution biological underlying mechanisms highlight potential targets

Язык: Английский

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Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries

Physiological Reviews, Год журнала: 2023, Номер 104(1), С. 473 - 532

Опубликована: Сен. 21, 2023

The normal stress response in humans is governed by the hypothalamic-pituitary-adrenal (HPA) axis through heightened mechanisms during stress, raising blood levels of glucocorticoid hormone cortisol. Glucocorticoids are quintessential compounds that balance proper functioning numerous systems mammalian body. They also generated synthetically and preeminent therapy for inflammatory diseases. act binding to nuclear receptor transcription factor (GR), which has two main isoforms (GRα GRβ). Our classical understanding signaling from GRα isoform, binds hormone, whereas GRβ no known ligands. With glucocorticoids being involved many physiological cellular processes, even small disruptions their release via HPA axis, or changes GR isoform expression, can have dire ramifications on health. Long-term chronic lead a glucocorticoid-resistant state, we deliberate how this impacts disease treatment. Chronic treatment noticeable side effects such as weight gain, adiposity, diabetes, others discuss detail. There sexually dimorphic responses glucocorticoids, women tend more hyperresponsive than men. This review summarizes our critically analyzes beneficial deleterious sexual differences cause dichotomy responses. We future propose new concept dual agonist postulate why activating both may prevent resistance.

Язык: Английский

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Xylazine suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is not altered by naloxone in rats.

Experimental and Clinical Psychopharmacology, Год журнала: 2023, Номер 32(2), С. 150 - 157

Опубликована: Июль 20, 2023

Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since is 100-fold more potent than morphine, its associated higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate xylazine, an anesthetic, increasingly detected in accidental deaths. Anecdotal suggest xylazine may prolong "high," alter onset withdrawal, increase resistance naloxone-induced reversal overdose. To date, no preclinical studies have evaluated impacts on self-administration (SA; 2.5 μg/kg/infusion) or withdrawal our knowledge. We established rat model xylazine/fentanyl co-SA outcomes as function biological sex. When administered alone, chronic (2.5 mg/kg, intraperitoneal) induced unique sex-specific symptomatology, whereby females showed delayed signs possible enhancement sensitivity motor-suppressing effects xylazine. Xylazine reduced consumption both male female rats regardless whether it was experimenter-administered added intravenous product (0.05, 0.10, 0.5 mg/kg/infusion) when compared SA alone. Interestingly, this effect dose-dependent self-administered intravenously. Naloxone (0.1 subcutaneous injection) did not somatic inclusion infusion either sex; however, were across time points after exposure following Together, these results dose-dependently suppressed intake sexes syndrome altered by acute treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Язык: Английский

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Neurosteroids and the mesocorticolimbic system

Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 153, С. 105356 - 105356

Опубликована: Авг. 10, 2023

Язык: Английский

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Sex steroid hormones, the estrous cycle, and rapid modulation of glutamatergic synapse properties in the striatal brain regions with a focus on 17β-estradiol and the nucleus accumbens

Steroids, Год журнала: 2023, Номер 201, С. 109344 - 109344

Опубликована: Ноя. 17, 2023

Язык: Английский

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Impacts of xylazine on fentanyl demand, body weight, and acute withdrawal in rats: A comparison to lofexidine

Neuropharmacology, Год журнала: 2023, Номер 245, С. 109816 - 109816

Опубликована: Дек. 20, 2023

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. health impacts of xylazine emerging raised alarm regarding public threat, warranting research on fentanyl's behavioral effects. No prior studies have evaluated effects consumption at various unit doses, demand, or withdrawal compared Food and Drug Administration-approved medication, lofexidine (Lucemyra®). This is important because are both adrenergic α2a (A2aR) agonists, however, not noted adulterant. Here we combined with self-administered doses male female rats body weight, acute withdrawal. Consumption alone increased saline. Xylazine but downward number suppressed demand intensity control group. Further, + reduced signs immediately following SA, by 12 h only co-exposed Weight loss occurred throughout SA regardless group, although group lost significantly more weight during first 24 than other two groups. Severity was also correlated severity somatic Together, these results suggest that may be indicator from xylazine/fentanyl combination, further translational evaluation.

Язык: Английский

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ERα Stimulation Rapidly Modulates Excitatory Synapse Properties in Female Rat Nucleus Accumbens Core

Neuroendocrinology, Год журнала: 2023, Номер 113(11), С. 1140 - 1153

Опубликована: Янв. 1, 2023

The nucleus accumbens core (NAcc) is a sexually differentiated brain region that modulated by steroid hormones such as 17β-estradiol (estradiol), with consequential impacts on relevant motivated behaviors and disorders addiction, anxiety, depression. NAcc estradiol levels naturally fluctuate, including during the estrous cycle in adult female rats, which analogous to menstrual humans. Across cycle, excitatory synapse properties of medium spiny neurons rapidly change, indicated analysis miniature postsynaptic currents (mEPSCs). mEPSC frequency decreases phases associated high levels. This decrease mimicked acute topical exposure estradiol. identity estrogen receptor (ER) underlying this action unknown. Adult rat expresses three ERs, all extranuclear: membrane ERα, ERβ, GPER1.In brief report, we take first step toward addressing challenge testing whether activation ERs via agonist application sufficient for inducing changes recorded whole-cell patch clamp.An ERα induced large frequency, while agonists ERβ GPER1 did not robustly modulate properties.These data provide evidence likely candidate estradiol-induced observed cycle. Overall, these findings extend our understanding neuroendocrinology implicate primary target future studies.

Язык: Английский

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The importance of translationally evaluating steroid hormone contributions to substance use

Frontiers in Neuroendocrinology, Год журнала: 2023, Номер 69, С. 101059 - 101059

Опубликована: Фев. 7, 2023

Clinically, women appear to be more susceptible certain aspects of substance use disorders (SUDs). The steroid hormones 17β-estradiol (E2) and progesterone (Pg) have been linked women-specific drug behaviors. Here, we review clinical preclinical studies investigating how cycling ovarian affect nicotine-, cocaine-, opioid-related We also highlight gaps in the literature regarding synthetic hormone may influence drug-related In addition, explore E2 Pg are known interact brain reward pathways provide evidence these interactions synthesis this demonstrates critical need study factors that SUDs, which play important roles addiction processes a sex-specific fashion. It is understand impact women's health key moving field forward toward efficacious individualized treatment strategies.

Язык: Английский

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Steroid Receptors and Coregulators: Dissemination of Sex Differences and Emerging Technologies

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108363 - 108363

Опубликована: Фев. 1, 2025

Steroid receptors are ligand-induced transcription factors that have broad functions among all living animal species, ranging from control of sex differences, body weight, stress responses, and many others. Their binding to coregulator proteins is regulated by corepressors coactivators interchange upon stimulation with a ligand. Coregulator an imperative understudied aspect steroid receptor signaling. Here, we discuss basics protein domain structures allow them interact coregulators other proteins, their essential as factors, elemental protein-protein interactions. We deliberate about the mechanisms in signaling, hormone signaling treatment opposite sex, how these affect complexes. The receptor-coregulator built-in components mammalian DNA mediate physiological everyday functions. Targeting crosstalk might be useful when imbalances lead disease. introduce novel technologies, such PamGene PamStation, make investigating heterogeneity complexes targeting more feasible. This review provides extensive understanding interactions intrinsic may offer therapeutic advantages.

Язык: Английский

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Associations between smoking and osteoporosis and all-cause mortality in participants from the United States: a cohort study

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Март 24, 2025

Background Smoking is a global public health concern, with approximately 1,245 billion smokers worldwide. It associated range of complications, including cardiovascular and respiratory diseases. Osteoporosis, characterized by reduced bone density deterioration tissue, has prevalence 18.3%, higher rates in women over the age 50. been recently osteoporosis, potentially due to shared metabolic disorders or personal habits. This study aimed investigate association between smoking osteoporosis relation all-cause mortality cohort from United States. Methods Data were sourced National Health Nutrition Examination Survey (NHANES) database, which focuses on individuals aged 20 years older 2005–2010, 2013–2014, 2017–2018, where femoral neck testing was conducted. The participants categorized basis their self-reported status mineral (BMD) measurements, following World Organization criteria for osteoporosis. covariates included age, sex, race, alcohol consumption, BMI, blood glucose levels, other indicators. Statistical analysis ANOVA chi-square tests baseline characteristics, Kaplan–Meier survival analysis, multivariate Cox regression assess hazard ratios (HRs) 95% confidence intervals (CIs) mortality. We divided patients into four different groups via cross-classification method whether they had Results 19,400 participants, significant differences characteristics across 4 (S-/OP+: nonsmokers osteoporosis; S+/OP-: without S-/OP-: S+/OP+: osteoporosis). overall average 53.1 years, accounted 49.6% total population. rate all factors population 13.1%, highest S+/OP+ rate. Participants both history 146% increase (HR: 2.46, CI: 2.12–2.87) even after adjusting confounding factors. relative excess risk interaction (RERI) suggested lack statistical significance, whereas attributable proportion (AP) indicated synergistic effect Conclusions highlights importance managing preventing reduce findings provide preliminary evidence risk, emphasizing need proactive strategies cessation close monitoring conditions.

Язык: Английский

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