scholarly journals Chronic Repeated Predatory Stress Induces Resistance to Quinine Adulteration of Ethanol in Male Mice

2019 ◽  
Author(s):  
Gladys A. Shaw ◽  
Maria Alexis M. Bent ◽  
Kimaya R. Council ◽  
A. Christian Pais ◽  
Ananda Amstadter ◽  
...  

AbstractBackgroundTrauma related psychiatric disorders, such as posttraumatic stress disorder (PTSD), and alcohol use disorder (AUD) are highly comorbid illnesses that separately present an opposing, sex-specific pattern, with increased prevalence of PTSD in females and increased prevalence of AUD diagnoses in males. Likewise, PTSD is a risk factor in the development of AUD, with conflicting data on the impact of sex in the comorbid development of both disorders. Because the likelihood of experiencing more than one traumatic event is high, we aim to utilize chronic repeated predatory stress (CRPS) to query the extent to which sex interacts with CRPS to influence alcohol consumption, or cessation of consumption.MethodsMale (n=16) and female (n=15) C57BL/6J mice underwent CRPS or daily handling for two weeks during adolescence (P35-P49) and two weeks during adulthood (P65-P79). Following the conclusion of two rounds of repeated stress, behavior was assessed in the open field. Mice subsequently underwent a two-bottle choice intermittent ethanol access (IEA) assessment (P90-131) with the options of 20% ethanol or water. After establishing drinking behavior, increasing concentrations of quinine were added to the ethanol to assess the drinking response to adulteration of the alcohol.ResultsCRPS increased fecal corticosterone concentrations and anxiety-like behaviors in the open field in both male and female mice as compared to control mice that had not been exposed to CRPS. Consistent with previous reports, we observed a sex difference in alcohol consumption such that females consumed more ethanol per gram of body mass than males. In addition, CRPS reduced alcohol aversion in male mice such that higher concentrations of quinine were necessary to reduce alcohol intake as compared to control mice. CRPS did not alter alcohol-related behaviors in female mice.ConclusionCollectively, we demonstrate that repeated CRPS can induce anxiety-like behavior in both sexes but selectively influences the response to ethanol adulteration in males.

2019 ◽  
Author(s):  
Margot C DeBaker ◽  
Janna K Moen ◽  
Jenna M Robinson ◽  
Kevin Wickman ◽  
Anna M Lee

AbstractRationaleAlcohol and nicotine addiction are prevalent conditions that co-occur. Despite the prevalence of co-use, factors that influence the suppression and enhancement of concurrent alcohol and nicotine intake are largely unknown.ObjectivesOur goals were to assess how nicotine abstinence and availability influenced concurrent alcohol consumption, and to determine the impact of quinine adulteration of alcohol on aversion resistant alcohol consumption and concurrent nicotine consumption.MethodsMale and female C57BL/6J mice voluntarily consumed unsweetened alcohol, nicotine and water in a chronic 3-bottle choice procedure. In Experiment 1, nicotine access was removed for 1 week and re-introduced the following week, while the alcohol and water bottles remained available at all times. In Experiment 2, quinine (100-1000 μM) was added to the 20% alcohol bottle, while the nicotine and water bottles remained unaltered.ResultsIn Experiment 1, we found that alcohol consumption and preference were unaffected by the presence or absence of nicotine access in both male and female mice. In Experiment 2a, we found that quinine temporarily suppressed alcohol intake and enhanced concurrent nicotine, but not water, preference in both male and female mice. In Experiment 2b, chronic quinine suppression of alcohol intake increased nicotine consumption and preference in female mice without affecting water preference, whereas it increased water and nicotine preference in male mice.ConclusionsQuinine suppression of alcohol consumption enhanced the preference for concurrent nicotine preference in male and female mice, suggesting that mice compensate for the quinine adulteration of alcohol by increasing their nicotine preference.


Author(s):  
Antoniette M. Maldonado-Devincci ◽  
Joseph G. Makdisi ◽  
Andrea M. Hill ◽  
Renee C. Waters ◽  
Nzia I. Hall ◽  
...  

AbstractWith alcohol readily accessible to adolescents, its consumption leads to many adverse effects, including impaired learning, attention, and behavior. Adolescents report higher rates of binge drinking compared to adults. Adolescents are also more prone to substance use disorder during adulthood due to physiological changes during the adolescent developmental period. We used C57BL/6J male and female mice to investigate the long-lasting impact of binge ethanol exposure during adolescence on voluntary ethanol intake and open field behavior during later adolescence and in young adulthood. The present set of experiments were divided into four stages: (1) chronic intermittent vapor inhalation exposure, (2) abstinence, (3) voluntary ethanol intake, and (4) open field behavioral testing. During adolescence, male and female mice were exposed to air or ethanol using an intermittent vapor inhalation with repeated binge pattern ethanol exposure from postnatal day (PND) 28–42. Following this, mice underwent abstinence during late adolescence from PND 43–49 (Experiment 1) or PND 43–69 (Experiment 2). Beginning on PND 49–76 (Experiment 1) or PND 70–97 (Experiment 2), mice were assessed for intermittent voluntary ethanol consumption using a two-bottle drinking procedure over 28 days. Male mice that were exposed to ethanol during adolescence showed increased ethanol consumption during later adolescence (Experiment 1) and in emerging adulthood (Experiment 2), while the female mice showed decreased ethanol consumption. These data demonstrate a sexually divergent shift in ethanol consumption following binge ethanol exposure during adolescence and differences in open field behavior. These data highlight sex-dependent vulnerability to developing substance use disorders in adulthood.Significance StatementCurrently, it is vital to determine the sex-dependent impact of binge alcohol exposure during adolescence, given that until recently females have largely been ignored. Here we show that adolescent male mice that are exposed to binge ethanol during adolescence show long-term changes in behavior in adulthood. In contrast, female mice show a transient decrease in ethanol consumption in adulthood and decreased motor activity spent in the center zone of the open field test. Male mice appear to be more susceptible to the long-term changes in ethanol consumption following binge ethanol exposure during adolescence.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Jianing Li ◽  
Ailing Ji ◽  
Ryan E Temel ◽  
Deneys R van der Westhuyzen ◽  
Gregory A Graf

Objective: The ABCG5 ABCG8 (G5G8) sterol transporter is the primary mechanism for biliary cholesterol secretion, but mice maintain fecal sterol excretion in its absence. The mechanism by which mice maintain sterol excretion in the absence of this pathway is not known. Transintestinal cholesterol excretion (TICE) is an alternative pathway to hepatobiliary secretion. We investigated the impact of G5G8 deficiency on TICE in the absence of Sitosterolemia. Methods and Results: We compared both hepatobiliary and transintestinal cholesterol excretion rates in wild-type (WT) and G5G8 deficient mice of both sexes. WT and G5G8 were maintained on a plant-sterol free diet from the time of weaning to prevent the development of secondary phenotypes associated with Sitosterolemia. Biliary and intestinal cholesterol secretion rates were determined by biliary diversion with simultaneous perfusion of the proximal 10 cm of the small bowel. Among WT mice, biliary cholesterol secretion was greater in female mice compared to males. Conversely, male mice exhibited greater rates of TICE than females. As expected, WT mice had higher biliary cholesterol secretion rates than their G5G8 deficient littermates. However, the decline in biliary cholesterol secretion was far less in male mice compared to females in the absence of G5G8. In female mice, the absence of G5G8 resulted in a two-fold increase in TICE, whereas males were unaffected. Conclusion: Female mice are more dependent upon the biliary pathway for cholesterol excretion, whereas males are more dependent upon TICE. G5G8 independent pathways are present for both biliary and intestinal cholesterol secretion. Female and male mice differ in their adaptation to G5G8 deficiency in order to maintain fecal sterol excretion.


2018 ◽  
Author(s):  
Angela M. Henricks ◽  
Lucas L. Dwiel ◽  
Nicholas H. Deveau ◽  
Amanda A. Simon ◽  
Metztli J. Ruiz-Jaquez ◽  
...  

AbstractIndividuals differ in their vulnerability to develop alcohol dependence that are determined by innate and environmental factors. The corticostriatal circuit is heavily involved in the development of alcohol dependence and may contain neural information regarding vulnerability to drink excessively. In the current experiment, we hypothesized that we could characterize high and low alcohol-drinking rats (HD and LD, respectively) based on corticostriatal oscillations, and that these subgroups would differentially respond to corticostriatal brain stimulation. Rats were trained to drink 10% alcohol in a limited access paradigm. In separate sessions, local field potentials (LFPs) were recorded from the nucleus accumbens shell (NAcSh) and medial prefrontal cortex (mPFC) of male Sprague-Dawley rats (n=13). Based on training alcohol consumption levels, we classified rats using a median split as HD or LD. Then, using machine-learning, we built predictive models to classify rats as HD or LD by corticostriatal LFPs and compared the model performance from real data to the performance of models built on data permutations. Additionally, we explored the impact of NAcSh or mPFC stimulation on alcohol consumption in HD vs. LD. Corticostriatal LFPs were able predict HD vs. LD group classification with greater accuracy than expected by chance (>80% accuracy). Additionally, NAcSh stimulation significantly reduced alcohol consumption in HD, but not LD (p<0.05), while mPFC stimulation did not alter drinking behavior in either HD or LD (p>0.05). These data collectively show that the corticostriatal circuit is differentially involved in regulating alcohol intake in HD vs. LD rats, and suggests that corticostriatal activity may have the potential to predict a vulnerability to develop alcohol dependence in a clinical population.


2021 ◽  
pp. 1-9
Author(s):  
Nicole Gehring ◽  
Carla Bettoni ◽  
Carsten A. Wagner ◽  
Isabel Rubio-Aliaga

<b><i>Introduction:</i></b> Phosphate homeostasis is regulated by a complex network involving the parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and calcitriol acting on several organs including the kidney, intestine, bone, and parathyroid gland. Previously, we showed that activation of the Janus kinase 1 (Jak1)-signal transducer and activator of transcription 3 (Stat3) signaling pathway leads to altered mineral metabolism with higher FGF23 levels, lower PTH, and higher calcitriol levels. Here, we investigated if there are sex differences in the role of Jak1/Stat3 signaling pathway on phosphate metabolism and if this pathway is sensitive to extracellular phosphate alterations. <b><i>Methods:</i></b> We used a mouse model (<i>Jak1</i><sup>S645P+/−</sup>) that resembles a constitutive activating mutation of the Jak1/Stat3 signaling pathway in humans and analyzed the impact of sex on mineral metabolism parameters. Furthermore, we challenged <i>Jak1</i><sup>S645P+/−</sup> male and female mice with a high (1.2% w/w) and low (0.1% w/w) phosphate diet and a diet with phosphate with organic origin with lower bioavailability. <b><i>Results:</i></b> Female mice, as male mice, showed higher intact FGF23 levels but no phosphaturia, and higher calcitriol and lower PTH levels in plasma. A phosphate challenge did not alter the effect of Jak1/Stat3 activation on phosphate metabolism for both genders. However, under a low phosphate diet or a diet with lower phosphate availability, the animals showed a tendency to develop hypophosphatemia. Moreover, male and female mice showed similar phosphate metabolism parameters. The only exception was higher PTH levels in male mice than those in females. <b><i>Discussion/Conclusion:</i></b> Sex and extracellular phosphate levels do not affect the impact of Jak1/Stat3 activation on phosphate metabolism.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Nada J. Habeichi ◽  
Ali Mroueh ◽  
Abdullah Kaplan ◽  
Rana Ghali ◽  
Hiam Al-Awassi ◽  
...  

Abstract The impact of cigarette smoking (CS) on kidney homeostasis in the presence of myocardial infarction (MI) in both males and females remains poorly elucidated. C57BL6/J mice were exposed to 2 weeks of CS prior to MI induction followed by 1 week of CS exposure in order to investigate the impact of CS on kidney damage in the presence of MI. Cardiac hemodynamic analysis revealed a significant decrease in ejection fraction (EF) in CS-exposed MI male mice when compared with the relative female subjects, whereas cardiac output (CO) comparably decreased in CS-exposed MI mice of both sexes. Kidney structural alterations, including glomerular retraction, proximal convoluted tubule (PCT) cross-sectional area, and total renal fibrosis were more pronounced in CS-exposed MI male mice when compared with the relative female group. Although renal reactive oxygen species (ROS) generation and glomerular DNA fragmentation significantly increased to the same extent in CS-exposed MI mice of both sexes, alpha-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) significantly increased in CS-exposed MI male mice, only. Metabolically, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide riboside-1 (NMRK-1) substantially increased in CS-exposed MI female mice only, whereas sirtuin (SIRT)-1 and SIRT-3 substantially decreased in CS-exposed MI male mice compared with their relative female group. Additionally, renal NAD levels significantly decreased only in CS-exposed MI male mice. In conclusion, MI female mice exhibited pronounced renal protection following CS when compared with the relative male groups.


Author(s):  
Zili Zhang ◽  
Rong Zheng

(1) Background: Many studies have shown that increasing taxation on cigarettes does play a role in tobacco control, but few studies have focused on whether increasing cigarette excise taxes significantly affects alcohol consumption. In this article, we aim to examine the effects of China’s 2015 increase in the cigarette excise tax on residents’ regular drinking behavior. (2) Methods: Using survey data from China Family Panel Studies (CFPS), we performed a panel logit regression analysis to model the relationship between the cigarette excise tax and regular drinking behavior. The Propensity Score Matching with Difference-in-Differences (PSM-DID) approach was adopted to determine the extent to which the cigarette excise tax affected residents’ drinking behavior. To test whether the cigarette excise tax could change regular drinking behavior by decreasing daily smoking quantity, we used an interaction term model. (3) Results: China’s 2015 increase in the cigarette excise tax had a significant negative effect on the probability of regular alcohol consumption among smokers, and the cigarette excise tax worked by reducing the average daily smoking of smokers. We also found that the regular drinking behavior of male smokers was more deeply affected by the increased cigarette excise tax than females. (4) Conclusions: Our research results not only give a deeper understanding of the impact of the cigarette excise tax, but also provide an important reference with which to guide future decisions concerning excise taxes imposed on cigarettes.


Endocrinology ◽  
2017 ◽  
Vol 158 (6) ◽  
pp. 1939-1950 ◽  
Author(s):  
Holger Henneicke ◽  
Jingbao Li ◽  
Sarah Kim ◽  
Sylvia J. Gasparini ◽  
Markus J. Seibel ◽  
...  

Abstract Chronic stress and depression are associated with alterations in the hypothalamic–pituitary–adrenal signaling cascade and considered a risk factor for bone loss and fractures. However, the mechanisms underlying the association between stress and poor bone health are unclear. Using a transgenic (tg) mouse model in which glucocorticoid signaling is selectively disrupted in mature osteoblasts and osteocytes [11β-hydroxysteroid-dehydrogenase type 2 (HSD2)OB-tg mice], the present study examines the impact of chronic stress on skeletal metabolism and structure. Eight-week-old male and female HSD2OB-tg mice and their wild-type (WT) littermates were exposed to chronic mild stress (CMS) for the duration of 4 weeks. At the endpoint, L3 vertebrae and tibiae were analyzed by micro–computed tomography and histomorphometry, and bone turnover was measured biochemically. Compared with nonstressed controls, exposure to CMS caused an approximately threefold increase in serum corticosterone concentrations in WT and HSD2OB-tg mice of both genders. Compared with controls, CMS resulted in loss of vertebral trabecular bone mass in male WT mice but not in male HSD2OB-tg littermates. Furthermore, both tibial cortical area and area fraction were reduced in stressed WT but not in stressed HSD2OB-tg male mice. Osteoclast activity and bone resorption marker were increased in WT males following CMS, features absent in HSD2OB-tg males. Interestingly, CMS had little effect on vertebral and long-bone structural parameters in female mice. We conclude that in male mice, bone loss during CMS is mediated via enhanced glucocorticoid signaling in osteoblasts (and osteocytes) and subsequent activation of osteoclasts. Female mice appear resistant to the skeletal effects of CMS.


2021 ◽  
Vol 9 ◽  
Author(s):  
Christine Wolter ◽  
Tino Lesener ◽  
Tobias Alexander Thomas ◽  
Alicia-Carolin Hentschel ◽  
Burkhard Gusy

Introduction: Heavy alcohol consumption constitutes a major health risk among University students. Social relationships with peers strongly affect University students' perception of the drinking behavior of others, which in turn plays a crucial role in determining their own alcohol intake. University students tend to overestimate their peers' alcohol consumption – a belief that is associated with an increase in an individual's own consumption. Therefore, we implemented a social norms intervention with personalized normative feedback at a major University in Germany to reduce and prevent excessive drinking among University students.Methods: Our intervention was part of a regular health monitoring survey. We invited all enrolled University students to take part in this survey on two occasions. A total of 862 University students completed the questionnaire, 563 (65.3%) of which received e-mail-based feedback upon request concerning their peers' and their own alcohol consumption. For the intervention group (n = 190) as well as the control group (no feedback requested; n = 101), we included only University students in the evaluation who overestimated their peers' alcohol use and indicated above average consumption of the peers. We applied analyses of variance to assess intervention effects with regard to the correction of overestimated group norms as well as University students' drinking behavior.Results: Within the intervention group, we observed a significantly larger reduction of the previously overestimated behavioral norms compared to the control group (p &lt; 0.001; ηp2 = 0.06). With regard to behavioral outcomes the intervention group showed a significantly larger reduction in the AUDIT-C score (p = 0.020; ηp2 = 0.03).Discussion: Our study confirms previous research whereupon personalized, gender-specific and selective normative feedback is effective for alcohol prevention among University students. However, University students still overestimated their peers' alcohol intake after the intervention. Furthermore, we did not reach high-risk groups (University students with the highest alcohol intake) since no feedback was requested. Future studies should address factors influencing the impact of the intervention and reachability of selective groups.


Author(s):  
Margarida Vasconcelos ◽  
Alberto Crego ◽  
Rui Rodrigues ◽  
Natália Almeida-Antunes ◽  
Eduardo López-Caneda

To “flatten the curve” of COVID-19 contagion, several countries ordered lockdowns amid the pandemic along with indications on social distancing. These social isolation measures could potentially bring alterations to healthy behavior, including to alcohol consumption. However, there is hardly any scientific evidence of the impact of such measures on alcohol consumption and binge drinking (BD) among young adults, and how they relate to alcohol craving, stress, anxiety, and depression levels. We addressed these questions by conducting a longitudinal study with 146 Portuguese college students—regular binge drinkers (regular BDs), infrequent binge drinkers (infrequent BDs) and non-binge drinkers (non-BDs)—in three moments: before the pandemic (Pre-Lockdown), during lockdown (Lockdown) and 6 months after (Post-Lockdown). Results revealed that regular BDs decreased alcohol use during Lockdown, a change in behavior that was even greater during Post-Lockdown, when regular BDs displayed similar levels of consumption to infrequent/non-BDs. Additionally, alcohol craving and living with friends were predictive of alcohol use during Lockdown, whereas stress, anxiety, and depression symptoms did not contribute to explain changes in drinking behavior. Collectively, the results suggest that BD in young Portuguese college students can be stopped when the contexts in which alcohol intake usually takes place are suppressed, which may have important implications for future prevention and intervention strategies.


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