Workplace harassment, stress, and drinking behavior over time: gender differences in a national sample

Research suggests that workplace harassment (WH) significantly predicts alcohol use and problem drinking behavior, but has generally failed to consider concurrent effects of other sources of stress. This two-wave study (n=1418) is the first to explore whether sexual harassment (SH) and generalized workplace harassment (GWH) predict increased drinking independently of the effects of job and life stress, and whether effects differ by gender, in a nationally representative sample. SH and GWH predicted increases in problem drinking one year later for men but not women, while life stress was associated with increased problem drinking for women but not men. This study confirms the importance of examining the associations between different types of stressors and drinking-related outcomes in gendered contexts.     

Variations in alcohol metabolism: influence of sex and age.

Alcohol-induced sleep time was measured subsequent to the intraperitoneal injection of a 3.5 g x kg-1 dose. The old male group had a sleep time approximately 4 times that of the young male group and approximately twice that of the old female group. Blood alcohol concentrations at time of awakening were nearly identical in all groups, indicating the difference in sleep time is not due to an altered CNS sensitivity. Measurement of in vivo alcohol disappearance rate indicates the old male group is different from the other groups because of a slower rate of alcohol metabolism. Although changes in hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were seen, the changes do not explain the observed decrease in alcohol metabolism observed in the old male group. These data provide further evidence that hepatic ADH and ALDH activities are not rate limiting in alcohol metabolism.     

Biological basis of sex differences in drug abuse: preclinical and clinical studies

The recent focus on drug abuse in women has brought attention to numerous differences between women and men. In this review, we discuss both preclinical and clinical findings of sex differences in drug abuse as well as mechanisms that may underlie these differences. Recent evidence suggests that the progression to dependence and abuse may differ between women and men; thus, different prevention and treatment strategies may be required. Similar sex differences in drug sensitivity and self-administration have been reported in laboratory animal studies. Females appear to be more vulnerable than males to the reinforcing effects of psychostimulants, opiates, and nicotine during many phases of the addiction process (e.g. acquisition, maintenance, dysregulation-escalation, relapse). Male and female animals differ in their behavioral, neurological, and pharmacological responses to drugs. Although the role of sex in the mechanisms of drug action remains unclear, preclinical and clinical studies indicate that ovarian hormones, particularly estrogen, play a role in producing sex differences in drug abuse. Future research is necessary to provide information on how to design more effective drug abuse treatment programs and resources that are sex specific. Electronic Publication     

Gender differences in drunk driving prevalence rates and trends: a 20-year assessment using multiple sources of evidence

This research tracked women's and men's drunk driving rates and the DUI sex ratio in the United States from 1982-2004 using three diverse sources of evidence. Sex-specific prevalence estimates and the sex ratio are derived from official arrest statistics from the Federal Bureau of Investigation, self-reports from the Centers for Disease Control and Prevention, and traffic fatality data from the National Highway and Transportation Safety Administration. Drunk driving trends were analyzed using Augmented Dickey Fuller time series techniques. Female DUI arrest rates increased whereas male rates declined then stabilized, producing a significantly narrower sex ratio. According to self-report and traffic data, women's and men's drunk driving rates declined and the gender gap was unchanged. Women's overrepresentation in arrests relative to their share of offending began in the 1990s and accelerated in 2000. Women's arrest gains, contrasted with no systematic change in DUI behavior, and the timing of this shift suggest an increased vulnerability to arrest. More stringent laws and enforcement directed at less intoxicated offenders may inadvertently target female offending patterns.     

An in vitro system for studying potential biological mechanisms of human sex differences in susceptibility to acute liver injury

Women are more susceptible than men to acute liver injury from drugs and other xenobiotics. The biological mechanisms for this sex difference are unknown, but known sex differences in steroid hormone levels and immune response could play a role. A human hepatocyte cell line, HepG2, was cultured for 8 days in either a male hormone, female hormone, or sex hormone-free medium. The cells were then exposed to a mixture of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, TNFα) for 72 h to simulate acute inflammation. Cell viability (total DNA) and various metabolic functions (reactive oxygen species (ROS), neutral and polar lipid (PL) accumulation, mitochondrial membrane potential, cytochrome P450 (CYP) activities) were measured fluorometrically. Acute phase proteins (albumin, IL-1ra) were measured in the culture medium by ELISA. This model gave both significant hormone only effects (ROS, PL accumulation) and cytokine only effects (total DNA, CYP1A, neutral and PL accumulation, albumin, IL-1ra) consistent with known biological responses. Significant hormone–cytokine interactions were observed for several endpoints (total DNA, ROS, neutral and PL accumulation, albumin). These findings suggest that sex hormones and pro-inflammatory cytokines can interact to alter liver metabolism in ways that may contribute to the marked sex difference in susceptibility to chemical-induced acute liver injury.     

Failure of dexamethasone to influence sex differences in acquisition of discriminated lever press avoidance

Discriminated lever press avoidance was used to test the hypothesis that higher plasma levels of pituitary-adrenocortical hormones in female rats can be held responsible for the superior active avoidance of female as compared to male rats. Male and female rats were administered dexamethasone (500 microg/kg body weight) during 4 days of avoidance acquisition and 1 additional day of extinction. This treatment resulted in a strong suppression of the pituitary-adrenocortical activity in both sexes. The corticosterone plasma level was very low, the adrenal weight was significantly reduced, but the pituitary weight was not affected. In other words, animals treated with dexamethasone were exposed to the lever press avoidance situation without a reactive pituitary-adrenocortical system. Under these conditions, sex differences in behavior were not affected and, therefore, the hypothesis that sex differences in pituitary-adrenocortical hormone levels contribute to sex differences in active avoidance, was not confirmed.     

Prenatal cocaine exposure, gender, and adolescent stress response: A prospective longitudinal study

Prenatal cocaine exposure is associated with alterations in arousal regulation in response to stress in young children. However, relations between cocaine exposure and stress response in adolescence have not been examined. We examined salivary cortisol, self-reported emotion, heart rate, and blood pressure (BP) responses to the Trier Social Stress Test (TSST) in 49 prenatally cocaine and other drug exposed (PCE) and 33 non-cocaine-exposed (NCE) adolescents. PCE adolescents had higher cortisol levels before and after stress exposure than NCE adolescents. PCE girls showed an elevated anxiety response to stress (compared to NCE girls) and PCE boys showed a dampened diastolic BP response (compared to NCE boys). Girls showed higher anger response and lower pre-stress systolic BP than boys. Group differences were found controlling for potential confounding variables and were not moderated by caregiver–child relationship quality (although relationship quality predicted HPA axis and anxiety response). The findings suggest that prenatal drug exposure is associated with altered stress response in adolescence and that gender moderates this association.     

Locomotor and stress responses to nicotine differ in adolescent and adult rats

Since adolescence is a critical period for the initiation of tobacco use, we have systematically compared behavioral and endocrine responses to nicotine in Sprague-Dawley rats of both sexes at early adolescence (postnatal day (P) 28), mid- adolescence (P38) and adulthood (P90). Locomotion and center time in a novel open field were evaluated for 30 min following intravenous injection of saline or nicotine (60 μg/kg), followed by measurement of plasma corticosterone. Complex age and sex differences in behavioral and endocrine response were observed, which were dependent on the functional endpoint examined. Whereas there were age differences in nicotine effects on all functional measures, sex differences were largely restricted to adult stress-related corticosterone and center-time responses. Although significant drug effects were detected at P28 and P90, there was no effect of nicotine at P38 on any measure examined. In saline-treated males, but not females, there were significant positive correlations across age between initial ambulatory counts and both initial vertical counts and total center time. Nicotine treatment increased correlations in both sexes, and yielded a significant negative interaction between initial ambulatory counts and plasma corticosterone. The unique responses of adolescents to nicotine are consistent with an immature function of nicotinic acetylcholine receptors at this age.     

Gonadectomy and sex differences in the behavioral responses to amphetamine and apomorphine of rats

Following treatment with 5 mg/kg d-amphetamine sulfate or 2 mg/kg apomorphine hydrochloride female rats displayed more intense and longer lasting stereotyped behavior than males. Gonadectomy did not affect the display of stereotyped behavior induced by either drug in either sex. A lower dose of amphetamine (1 mg/kg) caused greater stimulation of locomotor activity in females than in males. Castration of males had no effect, but ovariectomy blocked the stimulating effect of amphetamine on activity. By contrast, low doses of apomorphine depressed activity in a dose-dependent manner that was somewhat greater in ovariectomized females than in the other groups. These data add to the growing body of literature demonstrating that gonadal hormones modulate the activity of brain dopamine systems.     

性别因素对替利定及其代谢物去甲替利定在中国健康志愿者中药代动力学的影响(英文)

比较替利定和它的代谢物去甲替利定在不同性别中国健康志愿者中的药代动力学特征。9例（4例男性,5例女性）健康志愿者单次口服50 mg盐酸替利定口服液,在规定时间内采血,采用GC-NPD测定血药浓度,用非房室模型计算药代动力学参数。替利定和代谢物去甲替利定的主要动力学参数分别为:C_max（63.39±28.99）和（122.53±23.23）ng/mL;T_max（0.37±0.07）和（0.64±0.30）h;t_1/2（2.83±1.35）和（5.72±1.37）h;AUC_0-∞（101.59±41.85）和（577.13±189.77）ng·h/mL。替利定的男性和女性药动学参数分别为:C_max（73.88±40.88）和（55.01±15.16）ng/mL,T_max（0.37±0.08）和（0.36±0.08）h,t_1/2（4.05±1.07）和（1.86±0.41）h,AUC_0-∞（119.00±55.11）和（87.66±26.08）ng·h/mL。代谢物去甲替利定的男性和女性药动学参数分别为:C_max（108.82±27.88）和（133.49±12.56）ng/mL,T_max（0.94±0.13）和（0.40±0.09）h,t_1/2（4.66±1.18）和（6.57±0.84）h,AUC_0-∞（601.59±281.07）和（557.57±108.16）ng·h/mL。替利定的t_1/2男性比女性长,代谢物去甲替利定的T_max男性比女性慢,其它主要药代参数男性和女性之间没有统计学差异。受试者无严重不良事件发生,男性和女性的不良事件发生率有显著性差异。药代动力学研究显示,替利定口服液在应用于中国人时无需改变用药剂量,且性别因素影响不大。     

Lack of sex differences to the subjective effects of nitrous oxide in healthy volunteers

Background

Although numerous studies have assessed subjective effects of nitrous oxide, few studies have analyzed for sex differences. Since sex differences have been reported in subjective effects of several drugs such as opioids, nicotine and alcohol, we sought to determine if sex modulates the subjective effects of the inhalant, nitrous oxide, in healthy volunteers.

Methods

Thirty-eight females and seventy-two males from nine studies that were conducted in our laboratory were included in this retrospective analysis. All experimental studies utilized randomized, placebo-controlled, repeated measures designs in which subjects inhaled 30% nitrous oxide in oxygen and 100% oxygen (placebo). Dependent measures in this analysis were subjective effects measured at baseline and 15 min into the inhalation period.

Results

Nitrous oxide produced a number of subjective effects, including those that could be considered abuse liability-related (“elated,” “having pleasant thoughts,” drug liking), but sex did not modulate these effects.

Conclusions

Females and males showed similar subjective responses to 30% nitrous oxide. Future prospective studies might assess other concentrations, other measures (choice, analgesic response), and other inhaled general anesthetics to more comprehensively characterize the role of sex in response to inhalants.     

Sex differences and asymmetries of catecholamines: relation to turning preferences

Male and female Sprague-Dawley rats were tested for turning preferences in a multiple alley maze. The left and right caudate-putamen were dissected and assayed for norepinephrine and dopamine. Dopamine was not found to be lateralized contralateral to turning preference for females as a group. However, dopamine was significantly lateralized contralateral to the females turning preference if a strong turning bias was present. No relationship between dopamine asymmetry and turning preference was evident for males. Females were found to have norepinephrine significantly lateralized to the left caudate-putamen; in males greater striatal norepinephrine levels were equally distributed between left and right sides. This sexual dimorphism in norepinephrine lateralization was not related to turning preference.     

Nicotine modulates effects of stress on acoustic startle reflexes in rats: dependence on dose,stressor and initial reactivity

Cigarette smokers report that one reason for smoking is that smoking helps them cope with stress, but there is conflicting evidence as to whether nicotine reduces physiological and behavioral responses to stress. The acoustic startle reflex amplitude, pre-pulse inhibition, and habituation of the reflex provide quantifiable measures of behavioral reactivity that may be sensitive to stress-induced changes that are altered by nicotine. In the present experiment, rats classified as high and low reactors according to baseline startle amplitudes were administered nicotine (6 or 12 mg/kg/day) or saline by osmotic minipump for 11 days. On day 11, animals were acutely stressed by restraint or observation of restraint of conspecifics prior to startle measurement. Nicotine and stress each independently increased acoustic startle amplitude and amount of pre-pulse inhibition, but in combination, the effect of restraint stress and 12 mg/kg nicotine were indistinguishable from saline-treated, non-stressed controls. In contrast, the 6 mg/kg nicotine dose enhanced effects of both restraint and observation stressors on startle amplitude and pre-pulse inhibition. Animals classified as highly reactive prior to treatment were more responsive to nicotine, stress, and the combination, suggesting that initial reactivity is an important determinant of drug and stress effects. Results indicate that nicotine can both reduce and enhance stress effects on reflex amplitude and pre-pulse inhibition depending upon nicotine dose, stressor, and individual differences in reactivity.This research was supported by USUHS protocol RO72AR. The views contained herein are the private ones of the author and do not necessarily reflect those of the Uniformed Services University of the Health Sciences or the Department of Defense.     

Six-hydroxydopamine induced hyperactivity: neither sex differences nor caffeine stimulation are found

We investigated possible sex differences in the development of locomotor activity in rats treated neonatally with desmethylimipramine (DMI) followed by intraventricular 6-hydroxydopamine (6-HDA). In addition, the locomotor response to the stimulant caffeine was investigated in the male rats after they had reached adulthood. Both male and female 6-HDA-treated rats exhibited increased activity relative to controls. No sex differences were seen in either the development or magnitude of this effect. Male rats were used to determine the dose effects function for caffeine (0.5, 5, 15, 30 mg/kg) on locomotor activity. Control rats exhibited increased locomotor activity whereas 6-HDA-treated rats showed no increases with any dose of caffeine. Large decreases in the dopamine content of the olfactory tubercle (-88%, -82%), nucleus accumbens (-96%, -95%), and striatum (-99%, -99%) were found in both male and female rats. Choline acetyltransferase and glutamic acid decarboxylase activities were unchanged.     

Childhood Adversity and Hazardous Drinking: The Mediating Role of Attachment Insecurity

Background: Harmful alcohol use is associated with disease and mortality. Identifying new determinants of harmful drinking may aid the 16.3 million adults who have alcohol use disorders. Childhood adversity is associated with alcohol use, but is not amenable to change. Attachment insecurity (anxiety and avoidance) may be associated with alcohol use and may be a target for modification or used to personalize interventions. Objectives: This study aims to (a) identify the association between attachment insecurity and harmful drinking, (b) determine if attachment insecurity may mediate between childhood adversity and harmful drinking, and (c) test sex as a moderator between attachment insecurity and harmful drinking in the mediation relationship. Methods: Adult primary care patients (N = 348, 60% women) completed a cross-sectional survey study using validated measures in 2012. Statistical analyses were performed using Hayes's PROCESS macro in SPSS. Results: Childhood adversity was reported by 61% of the cohort and 18% endorsed harmful drinking. Attachment anxiety was associated with harmful drinking (p >.001), but attachment avoidance was not (p =.11). Attachment anxiety may mediate between childhood adversity and harmful drinking (95% CI:.03–.14). Sex did not moderate the relationships between attachment anxiety and harmful drinking in the mediation relationship (women: 95% CI:.031–.179; men: 95% CI:.003.–.182). Conclusions/Importance: Attachment anxiety may mediate between childhood adversity and harmful drinking in both men and women. Attachment anxiety may be a potential therapeutic target for people with a history of childhood adversity.     

The effects of novelty-seeking phenotypes and sex differences on acquisition of cocaine self-administration in selectively bred High-Responder and Low-Responder rats

Individual differences in exploratory behavior can predictably influence psychostimulant self-administration behavior. Male rats that exhibit a high degree of locomotor activity in a novel environment (High Responders, HR) will self-administer cocaine more readily than males exhibiting low levels of novelty-induced locomotion (Low Responders, LR). The present experiment investigates the combined influences of the sex of an individual and individual phenotypes in novelty-induced locomotion to predispose animals to acquire cocaine self-administration behavior, in male and female rats selectively bred for the HR-LR phenotypes. We first established that HR females, like their male counterparts, exhibit a dramatically greater locomotor response to novelty and less anxiety-like behavior than do LR females. While locomotor behavior was subtly influenced by estrous stage, with both HR and LR females showing increased activity during metestrus and diestrus compared to proestrus and estrus, the effect did not obscure HR-LR differences. When male and female HR-LR animals were trained to self-administer cocaine (2 h/day, 5 days/wk x 3 wk, 0.2 mg cocaine/kg/infusion), HR males and females acquired cocaine self-administration significantly faster than their LR counterparts. Furthermore, HR females self-administered significantly more cocaine than all other groups. In conclusion, female rats, like males, exhibit HR-LR phenotypes that predict rapidity of acquiring cocaine self-administration. Moreover, HR females self-administer more cocaine than HR males and both LR groups.     

Alcohol and tobacco use and heart rate reactivity to a psychosocial stressor in an adolescent population

Background

Few studies have investigated physiological stress (re)activity in relation to substance use, especially in adolescents. Using substances is one way to stimulate physiological arousal, therefore inherent hypo-arousal may be associated with substance use in adolescents. The purpose of this study was to examine the relation of autonomic nervous system (ANS) activity with alcohol and tobacco use in adolescents.

Methods

ANS activity and perceived stress during a social stress procedure were examined in relation to substance use. 275 Dutch adolescents from a general population study provided complete data. Heart rate was recorded continuously during a pre-task rest period, a stressful task period and a post-task recovery period. Alcohol and tobacco use were self-reported.

Results

Adolescents who consumed a medium and high number of alcoholic drinks per week (more than two) exhibited lower heart rates during the entire stress procedure as compared to those who consumed a low number of alcoholic drinks. Adolescents who smoked every day portrayed blunted heart rate reactivity to stress as compared to adolescents who smoked less frequently or not at all. Perceived stress was not related to alcohol or tobacco use.

Conclusions

Overall lower heart rate in adolescents who drank more and blunted heart rate reactivity to stress in those who used tobacco every day may indicate inherent hypo-arousal of the ANS system in those vulnerable to use substances more often. These adolescents may actively seek out substances in order to achieve a more normalized state of arousal.     

Husband's Level of Drinking and Egalitarianism in Mexican-American Families

This study examines the relationship between husband's level of drinking and his participation in traditionally defined female household duties. A quantity /frequency index of alcohol consumption was used to compare husband's drinking level with participation in child care, household cleaning, buying groceries, and cooking as a measure of egalitarianism in Mexican-American family households. Results show that husbands who abstain from alcohol participate in two of the household duties, cleaning and cooking, at significantly higher levels than either infrequent or frequent drinkers.     

Strain and sex alter effects of stress and nicotine on feeding, body weight, and HPA axis hormones

Gender and genotype result in differential sensitivity to stress and to nicotine. Male and female Sprague–Dawley and Long–Evans rats exhibit different behavioral responses to immobilization stress and to chronically-administered nicotine, suggesting that these animals may be useful to model human variability in stress and nicotine sensitivity. It is possible that differences in sensitivity of the hypothalamo–pituitary–adrenocortical (HPA) axis might account for these sex and strain differences. This experiment examined corticosterone (CORT) and adrenocorticotropin hormone (ACTH) responses of male and female Sprague–Dawley (n=117) and Long–Evans (n=120) rats administered 0, 6, or 12 mg/kg/day nicotine for 14 days; half of each treatment group was exposed to immobilization stress (20 min/day). Feeding and body weight also were measured. Nicotine increased CORT and ACTH levels of Sprague–Dawley females only. Stress increased CORT and ACTH levels of all groups except for Long–Evans females. Nicotine and stress decreased feeding and body weight with greatest effects in Long–Evans females. CORT, feeding, and body weight were positively correlated among stressed females. These findings suggest that strain differences in HPA axis, body weight, and feeding responses to nicotine and to stress are robust among females but not among males. CORT reactivity and female sex hormones may explain these differences.     

Age and sex differences in the locomotor effect of repeated methylphenidate in rats classified as high or low novelty responders

Rationale Rats displaying high levels of activity in an inescapable novel environment (high responders; HR) are more sensitive to the locomotor effect of stimulant drugs than rats displaying low levels of activity (low responders; LR).Objective The current study determined the age- and sex-dependent locomotor effects of repeated methylphenidate in HR and LR rats.Materials and methods Periadolescent and adult male and female Sprague–Dawley rats were first classified as HR or LR; rats were also classified as high or low novelty seekers based on free-choice preference for a novel environment. Locomotor activity was subsequently assessed after ten daily injections of methylphenidate (3 or 10 mg/kg s.c.) or saline. Fifteen days later, rats were challenged with saline and methylphenidate (10 mg/kg) over 2 days.Results During the repeated methylphenidate treatment phase, adult females showed greater methylphenidate-induced hyperactivity than adult males; there was no reliable difference in methylphenidate-induced hyperactivity between HR and LR rats of either age or sex. However, periadolescent male HR rats given repeated methylphenidate showed greater conditioned hyperactivity after the saline challenge than periadolescent male LR rats. Further, adult female HR rats given repeated methylphenidate showed greater conditioned hyperactivity and sensitization than adult female LR rats. In contrast, although free-choice novelty preference was greater among periadolescents than adults, individual differences in this variable did not predict the effect of repeated methylphenidate during any phase of the experiment.Conclusion Although individual differences in response to inescapable novelty predict methylphenidate-induced conditioned hyperactivity and sensitization, this relationship is moderated by age and sex.