Pub Date : 2018-07-01Epub Date: 2018-06-13DOI: 10.1111/acer.13768
Sandra W Jacobson, R Colin Carter, Christopher D Molteno, Ernesta M Meintjes, Marjanne S Senekal, Nadine M Lindinger, Neil C Dodge, Steven H Zeisel, Christopher P Duggan, Joseph L Jacobson
Background: Choline, an essential nutrient, serves as a methyl-group donor for DNA methylation and is a constituent of the neurotransmitter acetylcholine and a precursor to major components of cell membranes. Findings from animal studies suggest that choline supplementation during pregnancy can mitigate adverse effects of prenatal alcohol exposure on growth and neurocognitive function. We conducted a randomized, double-blind exploratory trial to examine feasibility and acceptability of a choline supplementation intervention during pregnancy.
Methods: Seventy heavy drinkers, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of 2 g of choline or a placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. Adherence was assessed by collecting used and unused drink packets on a monthly basis and tabulating the number used. Side effects were assessed in monthly interviews. Blood samples obtained at enrollment and at 4 and 12 weeks after randomization were assayed for plasma choline concentration.
Results: Adherence was good-to-excellent (median doses taken = 74.0%; interquartile range = 53.9 to 88.7%) and was not related to a range of sociodemographic characteristics or to alcohol consumption ascertained using a timeline follow-back interview. By 4 weeks, plasma choline concentrations were significantly higher in the choline supplementation than the placebo arm, and this group difference continued to be evident at 12 weeks. The only side effect was a small increase in nausea/dyspepsia. No effects were seen for diarrhea, vomiting, muscle stiffness, blood pressure, or body odor changes.
Conclusions: This study demonstrated that a choline supplementation program with very heavy drinkers during pregnancy is feasible even among highly disadvantaged, poorly educated women. The broad acceptability of this intervention is indicated by our finding that adherence was not related to maternal education, intellectual function, depression, nutritional status, or alcohol use.
{"title":"Feasibility and Acceptability of Maternal Choline Supplementation in Heavy Drinking Pregnant Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.","authors":"Sandra W Jacobson, R Colin Carter, Christopher D Molteno, Ernesta M Meintjes, Marjanne S Senekal, Nadine M Lindinger, Neil C Dodge, Steven H Zeisel, Christopher P Duggan, Joseph L Jacobson","doi":"10.1111/acer.13768","DOIUrl":"10.1111/acer.13768","url":null,"abstract":"<p><strong>Background: </strong>Choline, an essential nutrient, serves as a methyl-group donor for DNA methylation and is a constituent of the neurotransmitter acetylcholine and a precursor to major components of cell membranes. Findings from animal studies suggest that choline supplementation during pregnancy can mitigate adverse effects of prenatal alcohol exposure on growth and neurocognitive function. We conducted a randomized, double-blind exploratory trial to examine feasibility and acceptability of a choline supplementation intervention during pregnancy.</p><p><strong>Methods: </strong>Seventy heavy drinkers, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of 2 g of choline or a placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. Adherence was assessed by collecting used and unused drink packets on a monthly basis and tabulating the number used. Side effects were assessed in monthly interviews. Blood samples obtained at enrollment and at 4 and 12 weeks after randomization were assayed for plasma choline concentration.</p><p><strong>Results: </strong>Adherence was good-to-excellent (median doses taken = 74.0%; interquartile range = 53.9 to 88.7%) and was not related to a range of sociodemographic characteristics or to alcohol consumption ascertained using a timeline follow-back interview. By 4 weeks, plasma choline concentrations were significantly higher in the choline supplementation than the placebo arm, and this group difference continued to be evident at 12 weeks. The only side effect was a small increase in nausea/dyspepsia. No effects were seen for diarrhea, vomiting, muscle stiffness, blood pressure, or body odor changes.</p><p><strong>Conclusions: </strong>This study demonstrated that a choline supplementation program with very heavy drinkers during pregnancy is feasible even among highly disadvantaged, poorly educated women. The broad acceptability of this intervention is indicated by our finding that adherence was not related to maternal education, intellectual function, depression, nutritional status, or alcohol use.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028314/pdf/nihms965942.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36090176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-01Epub Date: 2018-06-09DOI: 10.1111/acer.13772
Katie Witkiewitz, Victoria R Votaw, Kevin E Vowles, Henry R Kranzler
Background: Alcohol is often consumed with opioids and alcohol misuse interferes with treatment for opioid use disorder (OUD). Drug misuse is associated with worse alcohol use disorder (AUD) treatment outcomes, yet no studies have investigated the role of opioid misuse in AUD treatment outcomes.
Methods: We conducted secondary analyses of the medication conditions of the COMBINE study (n = 1,226), a randomized clinical trial of medications (acamprosate and/or naltrexone) and behavioral interventions (medication management and/or behavioral intervention) for alcohol dependence. We examined associations between baseline opioid misuse and the use of cannabis and other drugs with time to first drinking day, time to first heavy drinking day, and the frequency and intensity of drinking during treatment and 1 year following treatment, based on latent profile analysis. Opioid misuse was defined as use of illicit or prescription opioids without a prescription or not as directed in the previous 6 months, in the absence of OUD. Self-reported cannabis and other drug use were also examined. Seventy individuals (5.7%) met the opioid misuse definition and 542 (44.2%) reported use of cannabis or other drugs without opioid misuse. We also examined medication adherence as a potential mediator.
Results: Baseline opioid misuse significantly predicted the time to first heavy drinking day (OR = 1.38 [95% CI: 1.13, 1.64], p = 0.001) and a higher probability of being in a heavier and more frequent drinking profile at the end of treatment (OR = 2.90 [95% CI: 1.43, 5.90], p = 0.003), and at 1 year following treatment (OR = 2.66 [95% CI: 1.26, 5.59], p = 0.01). Cannabis and other drug use also predicted outcomes. Medication adherence partially mediated the association between opioid misuse, cannabis use, other drug use, and treatment outcomes.
Conclusions: Opioid misuse and other drug use were associated with poorer AUD treatment outcomes, which was partially mediated by medication adherence. Clinicians and researchers should assess opioid misuse and other drug use in patients undergoing AUD treatment.
{"title":"Opioid Misuse as a Predictor of Alcohol Treatment Outcomes in the COMBINE Study: Mediation by Medication Adherence.","authors":"Katie Witkiewitz, Victoria R Votaw, Kevin E Vowles, Henry R Kranzler","doi":"10.1111/acer.13772","DOIUrl":"10.1111/acer.13772","url":null,"abstract":"<p><strong>Background: </strong>Alcohol is often consumed with opioids and alcohol misuse interferes with treatment for opioid use disorder (OUD). Drug misuse is associated with worse alcohol use disorder (AUD) treatment outcomes, yet no studies have investigated the role of opioid misuse in AUD treatment outcomes.</p><p><strong>Methods: </strong>We conducted secondary analyses of the medication conditions of the COMBINE study (n = 1,226), a randomized clinical trial of medications (acamprosate and/or naltrexone) and behavioral interventions (medication management and/or behavioral intervention) for alcohol dependence. We examined associations between baseline opioid misuse and the use of cannabis and other drugs with time to first drinking day, time to first heavy drinking day, and the frequency and intensity of drinking during treatment and 1 year following treatment, based on latent profile analysis. Opioid misuse was defined as use of illicit or prescription opioids without a prescription or not as directed in the previous 6 months, in the absence of OUD. Self-reported cannabis and other drug use were also examined. Seventy individuals (5.7%) met the opioid misuse definition and 542 (44.2%) reported use of cannabis or other drugs without opioid misuse. We also examined medication adherence as a potential mediator.</p><p><strong>Results: </strong>Baseline opioid misuse significantly predicted the time to first heavy drinking day (OR = 1.38 [95% CI: 1.13, 1.64], p = 0.001) and a higher probability of being in a heavier and more frequent drinking profile at the end of treatment (OR = 2.90 [95% CI: 1.43, 5.90], p = 0.003), and at 1 year following treatment (OR = 2.66 [95% CI: 1.26, 5.59], p = 0.01). Cannabis and other drug use also predicted outcomes. Medication adherence partially mediated the association between opioid misuse, cannabis use, other drug use, and treatment outcomes.</p><p><strong>Conclusions: </strong>Opioid misuse and other drug use were associated with poorer AUD treatment outcomes, which was partially mediated by medication adherence. Clinicians and researchers should assess opioid misuse and other drug use in patients undergoing AUD treatment.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.13772","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36196945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-01Epub Date: 2018-05-25DOI: 10.1111/acer.13759
Gentiana Sadikaj, D S Moskowitz
Background: Alcohol intoxication facilitates interpersonal aggression, but this effect depends on person and situation characteristics. Using the Alcohol Myopia Model, we examined the joint influence of alcohol, trait anger, and state anger on the association between perceived quarrelsomeness in an interaction partner and quarrelsome behavior in naturally occurring interpersonal interactions.
Methods: Using an event-contingent recording method over a 20-day period, community adults reported their perception of an interaction partner's quarrelsome behavior, their own anger and quarrelsome behavior, and the number of alcohol drinks consumed up to 3 hours prior to an interpersonal interaction.
Results: Results revealed that alcohol consumption and trait anger jointly moderated the association between perceived quarrelsomeness and quarrelsome behavior indirectly via state anger. Heightened anger experience accounted for increased quarrelsome behavior in response to perceived quarrelsomeness among higher trait anger individuals who reported increased alcohol consumption. When no alcohol was consumed, no such difference in quarrelsome behavioral response was found between low and high trait anger individuals.
Conclusions: Findings suggest that alcohol consumption may strengthen the influence of perceived quarrelsomeness on a person's own quarrelsome behavior among individuals with a readiness to experience anger. Intense anger experience may undermine these individuals' ability to inhibit aggressive behaviors when under the influence of alcohol.
{"title":"Alcohol Consumption and Trait Anger Strengthen the Association Between Perceived Quarrelsomeness and Quarrelsome Behavior via Feeling Angry.","authors":"Gentiana Sadikaj, D S Moskowitz","doi":"10.1111/acer.13759","DOIUrl":"https://doi.org/10.1111/acer.13759","url":null,"abstract":"<p><strong>Background: </strong>Alcohol intoxication facilitates interpersonal aggression, but this effect depends on person and situation characteristics. Using the Alcohol Myopia Model, we examined the joint influence of alcohol, trait anger, and state anger on the association between perceived quarrelsomeness in an interaction partner and quarrelsome behavior in naturally occurring interpersonal interactions.</p><p><strong>Methods: </strong>Using an event-contingent recording method over a 20-day period, community adults reported their perception of an interaction partner's quarrelsome behavior, their own anger and quarrelsome behavior, and the number of alcohol drinks consumed up to 3 hours prior to an interpersonal interaction.</p><p><strong>Results: </strong>Results revealed that alcohol consumption and trait anger jointly moderated the association between perceived quarrelsomeness and quarrelsome behavior indirectly via state anger. Heightened anger experience accounted for increased quarrelsome behavior in response to perceived quarrelsomeness among higher trait anger individuals who reported increased alcohol consumption. When no alcohol was consumed, no such difference in quarrelsome behavioral response was found between low and high trait anger individuals.</p><p><strong>Conclusions: </strong>Findings suggest that alcohol consumption may strengthen the influence of perceived quarrelsomeness on a person's own quarrelsome behavior among individuals with a readiness to experience anger. Intense anger experience may undermine these individuals' ability to inhibit aggressive behaviors when under the influence of alcohol.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.13759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36131132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-01Epub Date: 2018-06-06DOI: 10.1111/acer.13770
Suzanne M Colby, Lindsay Orchowski, Molly Magill, James G Murphy, Linda A Brazil, Timothy R Apodaca, Christopher W Kahler, Nancy P Barnett
Background: While there is a substantial literature on the efficacy of brief motivational intervention (BMI) for college student drinkers, research has focused less on young adults who do not attend a 4-year college, despite their elevated risk for excessive alcohol use and associated harmful consequences.
Methods: This randomized controlled trial (NCT01546025) compared the efficacy of BMI to a time-matched attention control intervention (relaxation training [REL]) for reducing alcohol consumption and related negative consequences in an underage young adult sample. BMI was tailored to the developmental transition out of high school for young adults who were not immediately planning to enroll in a 4-year college. Non-treatment-seeking underage drinkers who reported past-month heavy drinking (N = 167; ages 17 to 20; 42% female; 59% non-Hispanic White) were randomly assigned to receive a single session of BMI or REL. Outcomes were evaluated 6 weeks and 3 months postintervention via in-person assessments.
Results: Generalized estimating equation models provided strong support for the efficacy of BMI for reducing harmful drinking in these young adults. Compared to REL, and after controlling for baseline covariates including gender, those who received BMI subsequently reported significantly fewer average drinks per week, percent drinking days, percent heavy drinking days, lower peak and typical estimated blood alcohol concentration on drinking days, and fewer adverse consequences of drinking (all ps < 0.05). These between-group effects did not weaken over the course of the 3-month follow-up period.
Conclusions: These findings demonstrate an efficacious approach to tailoring BMI for non-college-attending young adults. Future research should replicate and extend these findings over a longer follow-up period.
{"title":"Brief Motivational Intervention for Underage Young Adult Drinkers: Results from a Randomized Clinical Trial.","authors":"Suzanne M Colby, Lindsay Orchowski, Molly Magill, James G Murphy, Linda A Brazil, Timothy R Apodaca, Christopher W Kahler, Nancy P Barnett","doi":"10.1111/acer.13770","DOIUrl":"https://doi.org/10.1111/acer.13770","url":null,"abstract":"<p><strong>Background: </strong>While there is a substantial literature on the efficacy of brief motivational intervention (BMI) for college student drinkers, research has focused less on young adults who do not attend a 4-year college, despite their elevated risk for excessive alcohol use and associated harmful consequences.</p><p><strong>Methods: </strong>This randomized controlled trial (NCT01546025) compared the efficacy of BMI to a time-matched attention control intervention (relaxation training [REL]) for reducing alcohol consumption and related negative consequences in an underage young adult sample. BMI was tailored to the developmental transition out of high school for young adults who were not immediately planning to enroll in a 4-year college. Non-treatment-seeking underage drinkers who reported past-month heavy drinking (N = 167; ages 17 to 20; 42% female; 59% non-Hispanic White) were randomly assigned to receive a single session of BMI or REL. Outcomes were evaluated 6 weeks and 3 months postintervention via in-person assessments.</p><p><strong>Results: </strong>Generalized estimating equation models provided strong support for the efficacy of BMI for reducing harmful drinking in these young adults. Compared to REL, and after controlling for baseline covariates including gender, those who received BMI subsequently reported significantly fewer average drinks per week, percent drinking days, percent heavy drinking days, lower peak and typical estimated blood alcohol concentration on drinking days, and fewer adverse consequences of drinking (all ps < 0.05). These between-group effects did not weaken over the course of the 3-month follow-up period.</p><p><strong>Conclusions: </strong>These findings demonstrate an efficacious approach to tailoring BMI for non-college-attending young adults. Future research should replicate and extend these findings over a longer follow-up period.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.13770","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36092290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-01Epub Date: 2018-06-04DOI: 10.1111/acer.13774
Samuel F Acuff, Kathryn E Soltis, Ashley A Dennhardt, Kristoffer S Berlin, James G Murphy
Background: Heavy drinking among college students is a significant public health concern that can lead to profound social and health consequences, including alcohol use disorder. Behavioral economics posits that low future orientation and high valuation of alcohol (alcohol demand) combined with deficits in alternative reinforcement increase the likelihood of alcohol misuse. Despite this, no study has examined the incremental utility of all 3 variables simultaneously in a comprehensive model.
Methods: This study uses structural equation modeling to test the associations between behavioral economic variables-alcohol demand (latent), future orientation (measured with a delay discounting task and the Consideration of Future Consequences [CFC] scale), and proportionate substance-related reinforcement-and alcohol consumption and problems among 393 heavy drinking college students. Two models are tested as follows: (i) an iteration of the reinforcer pathology model that includes an interaction between future orientation and alcohol demand; and (ii) an alternative model evaluating the interconnectedness of behavioral economic variables in predicting problematic alcohol use.
Results: The interaction effects in Model 1 were nonsignificant. Model 2 suggests that greater alcohol demand and proportionate substance-related reinforcement are associated with greater alcohol consumption and problems. Furthermore, CFC was associated with alcohol-related problems and lower proportionate substance-related reinforcement but was not significantly associated with alcohol consumption or alcohol demand. Finally, greater proportionate substance-related reinforcement was associated with greater alcohol demand.
Conclusions: Our results support the validity of the behavioral economic reinforcer pathology model as applied to young adult heavy drinking.
{"title":"Evaluating Behavioral Economic Models of Heavy Drinking Among College Students.","authors":"Samuel F Acuff, Kathryn E Soltis, Ashley A Dennhardt, Kristoffer S Berlin, James G Murphy","doi":"10.1111/acer.13774","DOIUrl":"https://doi.org/10.1111/acer.13774","url":null,"abstract":"<p><strong>Background: </strong>Heavy drinking among college students is a significant public health concern that can lead to profound social and health consequences, including alcohol use disorder. Behavioral economics posits that low future orientation and high valuation of alcohol (alcohol demand) combined with deficits in alternative reinforcement increase the likelihood of alcohol misuse. Despite this, no study has examined the incremental utility of all 3 variables simultaneously in a comprehensive model.</p><p><strong>Methods: </strong>This study uses structural equation modeling to test the associations between behavioral economic variables-alcohol demand (latent), future orientation (measured with a delay discounting task and the Consideration of Future Consequences [CFC] scale), and proportionate substance-related reinforcement-and alcohol consumption and problems among 393 heavy drinking college students. Two models are tested as follows: (i) an iteration of the reinforcer pathology model that includes an interaction between future orientation and alcohol demand; and (ii) an alternative model evaluating the interconnectedness of behavioral economic variables in predicting problematic alcohol use.</p><p><strong>Results: </strong>The interaction effects in Model 1 were nonsignificant. Model 2 suggests that greater alcohol demand and proportionate substance-related reinforcement are associated with greater alcohol consumption and problems. Furthermore, CFC was associated with alcohol-related problems and lower proportionate substance-related reinforcement but was not significantly associated with alcohol consumption or alcohol demand. Finally, greater proportionate substance-related reinforcement was associated with greater alcohol demand.</p><p><strong>Conclusions: </strong>Our results support the validity of the behavioral economic reinforcer pathology model as applied to young adult heavy drinking.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.13774","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36095731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-01Epub Date: 2018-05-21DOI: 10.1111/acer.13760
Harpreet Sidhu, Max Kreifeldt, Candice Contet
Background: Alcohol use disorders are characterized by a complex behavioral symptomatology, which includes the loss of control over alcohol consumption and the emergence of a negative affective state when alcohol is not consumed. Some of these symptoms can be recapitulated in rodent models, for instance following chronic intermittent ethanol (EtOH; CIE) vapor inhalation. However, the detection of negative affect in mice withdrawn from CIE has proven challenging and variable between strains. This study aimed to detect reliable indices of negative emotionality in CIE-exposed C57BL/6J (C57) and DBA/2J (DBA) mice. Males were used because they are known to escalate their voluntary EtOH consumption upon CIE exposure, which is hypothesized to be driven by negative reinforcement (relief from negative affect).
Methods: Adult male mice were exposed to 4 to 6 weeks of CIE and were evaluated 3 to 10 days into withdrawal in the social approach, novelty-suppressed feeding, digging, marble burying, and bottle brush tests.
Results: Withdrawal from CIE decreased sociability in DBA mice but not in C57 mice. Conversely, hyponeophagia was exacerbated by CIE in C57 mice but not in DBA mice. Withdrawal from CIE robustly increased digging activity in both strains, even in the absence of marbles. Aggressive responses to bottle brush attacks were elevated in both C57 and DBA mice following CIE exposure, but CIE had an opposite effect on defensive responses in the 2 strains (increase in C57 vs. decrease in DBA).
Conclusions: Our results indicate that withdrawal from CIE elicits negative emotionality in both C57 and DBA mice, but different tests need to be used to measure the anxiogenic-like effects of withdrawal in each strain. Increased digging activity and irritability-like behavior represent novel indices of affective dysfunction associated with withdrawal from CIE in both mouse strains. Our findings enrich the characterization of the affective symptomatology of protracted withdrawal from CIE in mice.
{"title":"Affective Disturbances During Withdrawal from Chronic Intermittent Ethanol Inhalation in C57BL/6J and DBA/2J Male Mice.","authors":"Harpreet Sidhu, Max Kreifeldt, Candice Contet","doi":"10.1111/acer.13760","DOIUrl":"10.1111/acer.13760","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorders are characterized by a complex behavioral symptomatology, which includes the loss of control over alcohol consumption and the emergence of a negative affective state when alcohol is not consumed. Some of these symptoms can be recapitulated in rodent models, for instance following chronic intermittent ethanol (EtOH; CIE) vapor inhalation. However, the detection of negative affect in mice withdrawn from CIE has proven challenging and variable between strains. This study aimed to detect reliable indices of negative emotionality in CIE-exposed C57BL/6J (C57) and DBA/2J (DBA) mice. Males were used because they are known to escalate their voluntary EtOH consumption upon CIE exposure, which is hypothesized to be driven by negative reinforcement (relief from negative affect).</p><p><strong>Methods: </strong>Adult male mice were exposed to 4 to 6 weeks of CIE and were evaluated 3 to 10 days into withdrawal in the social approach, novelty-suppressed feeding, digging, marble burying, and bottle brush tests.</p><p><strong>Results: </strong>Withdrawal from CIE decreased sociability in DBA mice but not in C57 mice. Conversely, hyponeophagia was exacerbated by CIE in C57 mice but not in DBA mice. Withdrawal from CIE robustly increased digging activity in both strains, even in the absence of marbles. Aggressive responses to bottle brush attacks were elevated in both C57 and DBA mice following CIE exposure, but CIE had an opposite effect on defensive responses in the 2 strains (increase in C57 vs. decrease in DBA).</p><p><strong>Conclusions: </strong>Our results indicate that withdrawal from CIE elicits negative emotionality in both C57 and DBA mice, but different tests need to be used to measure the anxiogenic-like effects of withdrawal in each strain. Increased digging activity and irritability-like behavior represent novel indices of affective dysfunction associated with withdrawal from CIE in both mouse strains. Our findings enrich the characterization of the affective symptomatology of protracted withdrawal from CIE in mice.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028290/pdf/nihms962440.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36036012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Beaudet, S. Valable, J. Bourgine, V. Lelong-Boulouard, L. Lanfumey, T. Freret, M. Boulouard, E. Paizanis
BACKGROUND Binge drinking is popular and highly prevalent in teenagers. However, the long-term cognitive and neurobiological consequences of such practices are not yet fully understood. In this context, we therefore assessed in mice whether a chronic intermittent alcohol (CIA) exposure in adolescence had long-term consequences on object discrimination and memory performances, emotional behaviors, brain activity, and morphology. METHODS C57BL/6JRj mice were treated with either saline or ethanol (EtOH) (2 g/kg/d, i.p., from postnatal days [PND] 30 to PND 44 every other day). The day following the last administration or later in adulthood (PND 71) mice were tested for different behavioral tests (novel object recognition, spontaneous alternation, light-dark box, elevated plus-maze, actimeter test), to assess object recognition, working memory performances, anxiety-like behavior, and locomotor activity. We also investigated neuronal activation of hippocampus, prefrontal and perirhinal cortices, and anatomical changes using immediate-early gene expression and longitudinal brain magnetic resonance imaging. RESULTS Our results showed that adolescent mice exposed to CIA present a critical and persistent impairment of short-term object recognition performances. By contrast, spatial working memory was not impaired, nor was anxiety-like behavior. This altered object discrimination was associated with a biphasic change in neuronal activity in the hippocampus but without morphological changes. Indeed, c-Fos expression was specifically increased in the dorsal dentate gyrus (DG) of the hippocampus after the binge exposure, but then became significantly lower in adulthood both in the DG and the CA1 part of the hippocampus compared with adult saline pretreated mice. CONCLUSIONS These findings provide evidence for adolescent vulnerability to the effects of intermittent binge EtOH exposure on object discrimination and hippocampal activity with long-lasting consequences.
{"title":"Long-Lasting Effects of Chronic Intermittent Alcohol Exposure in Adolescent Mice on Object Recognition and Hippocampal Neuronal Activity.","authors":"G. Beaudet, S. Valable, J. Bourgine, V. Lelong-Boulouard, L. Lanfumey, T. Freret, M. Boulouard, E. Paizanis","doi":"10.1111/acer.13256","DOIUrl":"https://doi.org/10.1111/acer.13256","url":null,"abstract":"BACKGROUND\u0000Binge drinking is popular and highly prevalent in teenagers. However, the long-term cognitive and neurobiological consequences of such practices are not yet fully understood. In this context, we therefore assessed in mice whether a chronic intermittent alcohol (CIA) exposure in adolescence had long-term consequences on object discrimination and memory performances, emotional behaviors, brain activity, and morphology.\u0000\u0000\u0000METHODS\u0000C57BL/6JRj mice were treated with either saline or ethanol (EtOH) (2 g/kg/d, i.p., from postnatal days [PND] 30 to PND 44 every other day). The day following the last administration or later in adulthood (PND 71) mice were tested for different behavioral tests (novel object recognition, spontaneous alternation, light-dark box, elevated plus-maze, actimeter test), to assess object recognition, working memory performances, anxiety-like behavior, and locomotor activity. We also investigated neuronal activation of hippocampus, prefrontal and perirhinal cortices, and anatomical changes using immediate-early gene expression and longitudinal brain magnetic resonance imaging.\u0000\u0000\u0000RESULTS\u0000Our results showed that adolescent mice exposed to CIA present a critical and persistent impairment of short-term object recognition performances. By contrast, spatial working memory was not impaired, nor was anxiety-like behavior. This altered object discrimination was associated with a biphasic change in neuronal activity in the hippocampus but without morphological changes. Indeed, c-Fos expression was specifically increased in the dorsal dentate gyrus (DG) of the hippocampus after the binge exposure, but then became significantly lower in adulthood both in the DG and the CA1 part of the hippocampus compared with adult saline pretreated mice.\u0000\u0000\u0000CONCLUSIONS\u0000These findings provide evidence for adolescent vulnerability to the effects of intermittent binge EtOH exposure on object discrimination and hippocampal activity with long-lasting consequences.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73024858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND Driver age and blood alcohol concentration are both important factors in predicting driving risk; however, little is known regarding the joint import of these factors on neural activity following socially relevant alcohol doses. We examined age and alcohol effects on brain oscillations during simulated driving, focusing on 2 region-specific frequency bands implicated in task performance and attention: parietal alpha power (PAP; 8 to 12 Hz) and frontal theta power (FTP; 4 to 7 Hz). METHODS Participants included 80 younger (aged 25 to 35 years) and 40 older (aged 55 to 70 years) community-dwelling, moderate drinkers. Participants consumed placebo, low, or moderate doses of alcohol designed to achieve target peak breath alcohol concentrations of 0, 0.04, or 0.065 g/dl, respectively. Electrophysiological measures were recorded during engagement in a simulated driving task involving 4 scenarios of varied environmental complexity. RESULTS A main effect of age was detected in FTP, but neither an alcohol effect nor interactions were observed. For PAP, an age-by-alcohol interaction was detected. Relative to placebo controls, older and younger participants receiving low-dose (0.04 g/dl) alcohol evinced divergent PAP alterations, with a pattern of higher power among older participants and lower power among younger participants. This interaction was noted across the varied environmental contexts. CONCLUSIONS These findings are consistent with the hypothesis that compared with younger individuals, older drivers may be differentially susceptible to alcohol effects. While these age-by-alcohol interactions in neural activity are provocative, further investigation exploring the mechanisms and behavioral correlates of these effects will be crucial in determining their behavioral impact.
{"title":"Effects of Age and Acute Moderate Alcohol Administration on Neurophysiology During Simulated Driving.","authors":"B. Lewis, J. Boissoneault, I. Frazier, S. Nixon","doi":"10.1111/acer.13243","DOIUrl":"https://doi.org/10.1111/acer.13243","url":null,"abstract":"BACKGROUND\u0000Driver age and blood alcohol concentration are both important factors in predicting driving risk; however, little is known regarding the joint import of these factors on neural activity following socially relevant alcohol doses. We examined age and alcohol effects on brain oscillations during simulated driving, focusing on 2 region-specific frequency bands implicated in task performance and attention: parietal alpha power (PAP; 8 to 12 Hz) and frontal theta power (FTP; 4 to 7 Hz).\u0000\u0000\u0000METHODS\u0000Participants included 80 younger (aged 25 to 35 years) and 40 older (aged 55 to 70 years) community-dwelling, moderate drinkers. Participants consumed placebo, low, or moderate doses of alcohol designed to achieve target peak breath alcohol concentrations of 0, 0.04, or 0.065 g/dl, respectively. Electrophysiological measures were recorded during engagement in a simulated driving task involving 4 scenarios of varied environmental complexity.\u0000\u0000\u0000RESULTS\u0000A main effect of age was detected in FTP, but neither an alcohol effect nor interactions were observed. For PAP, an age-by-alcohol interaction was detected. Relative to placebo controls, older and younger participants receiving low-dose (0.04 g/dl) alcohol evinced divergent PAP alterations, with a pattern of higher power among older participants and lower power among younger participants. This interaction was noted across the varied environmental contexts.\u0000\u0000\u0000CONCLUSIONS\u0000These findings are consistent with the hypothesis that compared with younger individuals, older drivers may be differentially susceptible to alcohol effects. While these age-by-alcohol interactions in neural activity are provocative, further investigation exploring the mechanisms and behavioral correlates of these effects will be crucial in determining their behavioral impact.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85452184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Thompson, N. Hill-Kapturczak, M. Lopez-Cruzan, L. Alvarado, A. Dwivedi, M. Javors
BACKGROUND Phosphatidylethanol (PEth) is a metabolite of ethanol (EtOH), and its concentration in whole blood samples is a direct biomarker of alcohol consumption. Because PEth is also present in the brain and incorporated in lipid membranes, it can be used to classify deceased individuals on alcohol consumption status at the time of death. The purpose of this study was to detect PEth homologs in postmortem brains of individuals known to have had alcohol use disorder (AUD) and to determine the relationship between serum alcohol at the time of death and PEth in the cerebellum (CE) and orbital frontal cortex (OFC). METHODS Postmortem brain was collected and stored according to standard protocol. Psychiatric symptoms experienced prior to death were obtained by next of kin psychological autopsy to categorize subjects. Thirty male subjects were chosen for analyses: 10 with AUD with positive serum EtOH levels present at time of autopsy (AUD-W), 10 with AUD without positive serum EtOH levels (AUD-WO), and 10 controls. PEth 16:0/18:1 and 16:0/18:2 were quantified in 50 mg of CE and OFC of human postmortem brain using HPLC and mass spectrometric detection (triple quadrupole). RESULTS Results of this study were as follows: (i) PEth 16:0/18:1 and 16:0/18:2 were detected in the CE and OFC of all subjects diagnosed with AUD, (ii) PEth 16:0/18:1 levels were about 10-fold higher than PEth 16:0/18:2 in all subjects and both areas of brain, (iii) AUD-W subjects had higher PEth homolog levels in CE and OFC than controls and AUD-WO subjects, (iv) PEth 16:0/18:1, but not PEth 16:0/18:2, levels in CE and OFC of AUD-W subjects correlated significantly with serum EtOH levels at the time of death. CONCLUSIONS Quantification of combined PEth homolog levels in postmortem human brain is a good candidate as a diagnostic factor to classify drinking status, especially for those with AUD at the time of death. For alcohol research studies with postmortem brain, verification of drinking status is essential.
{"title":"Phosphatidylethanol in Postmortem Brain and Serum Ethanol at Time of Death.","authors":"P. Thompson, N. Hill-Kapturczak, M. Lopez-Cruzan, L. Alvarado, A. Dwivedi, M. Javors","doi":"10.1111/acer.13254","DOIUrl":"https://doi.org/10.1111/acer.13254","url":null,"abstract":"BACKGROUND\u0000Phosphatidylethanol (PEth) is a metabolite of ethanol (EtOH), and its concentration in whole blood samples is a direct biomarker of alcohol consumption. Because PEth is also present in the brain and incorporated in lipid membranes, it can be used to classify deceased individuals on alcohol consumption status at the time of death. The purpose of this study was to detect PEth homologs in postmortem brains of individuals known to have had alcohol use disorder (AUD) and to determine the relationship between serum alcohol at the time of death and PEth in the cerebellum (CE) and orbital frontal cortex (OFC).\u0000\u0000\u0000METHODS\u0000Postmortem brain was collected and stored according to standard protocol. Psychiatric symptoms experienced prior to death were obtained by next of kin psychological autopsy to categorize subjects. Thirty male subjects were chosen for analyses: 10 with AUD with positive serum EtOH levels present at time of autopsy (AUD-W), 10 with AUD without positive serum EtOH levels (AUD-WO), and 10 controls. PEth 16:0/18:1 and 16:0/18:2 were quantified in 50 mg of CE and OFC of human postmortem brain using HPLC and mass spectrometric detection (triple quadrupole).\u0000\u0000\u0000RESULTS\u0000Results of this study were as follows: (i) PEth 16:0/18:1 and 16:0/18:2 were detected in the CE and OFC of all subjects diagnosed with AUD, (ii) PEth 16:0/18:1 levels were about 10-fold higher than PEth 16:0/18:2 in all subjects and both areas of brain, (iii) AUD-W subjects had higher PEth homolog levels in CE and OFC than controls and AUD-WO subjects, (iv) PEth 16:0/18:1, but not PEth 16:0/18:2, levels in CE and OFC of AUD-W subjects correlated significantly with serum EtOH levels at the time of death.\u0000\u0000\u0000CONCLUSIONS\u0000Quantification of combined PEth homolog levels in postmortem human brain is a good candidate as a diagnostic factor to classify drinking status, especially for those with AUD at the time of death. For alcohol research studies with postmortem brain, verification of drinking status is essential.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82325809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Bergeson, Michelle A. Nipper, Jeremiah P. Jensen, M. Helms, D. Finn
BACKGROUND The chronic intermittent ethanol (CIE) paradigm is valuable for screening compounds for efficacy to reduce drinking traits related to alcohol use disorder (AUD), as it measures alcohol consumption and preference under physical dependence conditions. Air control-treated animals allow simultaneous testing of similarly treated, nondependent animals. As a consequence, we used CIE to test the hypothesis that tigecycline, a semisynthetic tetracycline similar to minocycline and doxycycline, would reduce alcohol consumption regardless of dependence status. METHODS Adult C57BL/6J female and male mice were tested for tigecycline efficacy to reduce ethanol (EtOH) consumption using a standard CIE paradigm. The ability of tigecycline to decrease 2-bottle choice of 15% EtOH (15E) versus water intake in dependent (CIE vapor) and nondependent (air-treated) male and female mice was tested after 4 cycles of CIE vapor or air exposure using a within-subjects design and a dose-response. Drug doses of 0, 40, 60, 80, and 100 mg/kg in saline were administered intraperitoneally (0.01 ml/g body weight) and in random order, with a 1-hour pretreatment time. Baseline 15E intake was re-established prior to administration of subsequent injections, with a maximum of 2 drug injections tested per week. RESULTS Tigecycline was found to effectively reduce high alcohol consumption in both dependent and nondependent female and male mice. CONCLUSIONS Our data suggest that tigecycline may be a promising drug with novel pharmacotherapeutic characteristics for the treatment of mild-to-severe AUD in both sexes.
{"title":"Tigecycline Reduces Ethanol Intake in Dependent and Nondependent Male and Female C57BL/6J Mice.","authors":"S. Bergeson, Michelle A. Nipper, Jeremiah P. Jensen, M. Helms, D. Finn","doi":"10.1111/acer.13251","DOIUrl":"https://doi.org/10.1111/acer.13251","url":null,"abstract":"BACKGROUND\u0000The chronic intermittent ethanol (CIE) paradigm is valuable for screening compounds for efficacy to reduce drinking traits related to alcohol use disorder (AUD), as it measures alcohol consumption and preference under physical dependence conditions. Air control-treated animals allow simultaneous testing of similarly treated, nondependent animals. As a consequence, we used CIE to test the hypothesis that tigecycline, a semisynthetic tetracycline similar to minocycline and doxycycline, would reduce alcohol consumption regardless of dependence status.\u0000\u0000\u0000METHODS\u0000Adult C57BL/6J female and male mice were tested for tigecycline efficacy to reduce ethanol (EtOH) consumption using a standard CIE paradigm. The ability of tigecycline to decrease 2-bottle choice of 15% EtOH (15E) versus water intake in dependent (CIE vapor) and nondependent (air-treated) male and female mice was tested after 4 cycles of CIE vapor or air exposure using a within-subjects design and a dose-response. Drug doses of 0, 40, 60, 80, and 100 mg/kg in saline were administered intraperitoneally (0.01 ml/g body weight) and in random order, with a 1-hour pretreatment time. Baseline 15E intake was re-established prior to administration of subsequent injections, with a maximum of 2 drug injections tested per week.\u0000\u0000\u0000RESULTS\u0000Tigecycline was found to effectively reduce high alcohol consumption in both dependent and nondependent female and male mice.\u0000\u0000\u0000CONCLUSIONS\u0000Our data suggest that tigecycline may be a promising drug with novel pharmacotherapeutic characteristics for the treatment of mild-to-severe AUD in both sexes.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83118229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}