The Experts below are selected from a list of 2304 Experts worldwide ranked by ideXlab platform
Ryan Y. Wong - One of the best experts on this subject based on the ideXlab platform.
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Differential effects of ethanol on behavior and GABAA receptor expression in adult zebrafish (Danio rerio) with alternative stress coping styles.
Scientific reports, 2020Co-Authors: Alexander C. Goodman, Ryan Y. WongAbstract:Variation in stress responses between individuals are linked to factors ranging from stress coping styles to sensitivity of neurotransmitter systems. Many anxiolytic compounds (e.g. ethanol) can increase stressor engagement through modulation of neurotransmitter systems and are used to investigate stress response mechanisms. There are two alternative suites of correlated behavioral and physiological responses to stressors (stress coping styles) that differ in exploration tendencies: proactive and reactive stress coping styles. By chronically treating individuals differing in stress coping style with ethanol, a GABA-acting drug, we assessed the role of the GABAergic system on the behavioral stress response. Specifically, we investigated resulting changes in stress-related behavior (i.e. exploratory behavior) and whole-brain GABAA receptor subunits (gabra1, GABRA2, gabrd, & gabrg2) in response to a novelty stressor. We found that ethanol-treated proactive individuals showed lower stress-related behaviors than their reactive counterparts. Proactive individuals showed significantly higher expression of gabra1, GABRA2, and gabrg2 compared to reactive individuals and ethanol treatment resulted in upregulation of gabra1 and gabrg2 in both stress coping styles. These results suggest that impacts of ethanol on stress-related behaviors vary by stress coping style and that expression of select GABAA receptor subunits may be one of the underlying mechanisms.
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Differential effects of ethanol on behavior and GABAA receptor subunit expression in zebrafish (Danio rerio) with alternative stress coping styles
2019Co-Authors: Alexander C. Goodman, Ryan Y. WongAbstract:Variation in stress responses between individuals is linked to factors ranging from stress coping styles to sensitivity of neurotransmitter systems. Many anxiolytic compounds (e.g. ethanol) can increase stressor engagement through modulation of neurotransmitter systems and are used to investigate stress response mechanisms. Here we assessed the role of the GABAA system on the variation of the behavioral stress response by comparing individuals differing in stress coping styles that were chronically treated with ethanol. Specifically, we investigated resulting changes in stress-related behavior and whole-brain GABAA receptor subunits (gabra1, GABRA2, gabrd, & gabrg2) in response to a novelty stressor. There were significant main and interaction effects on two stress-related behaviors, where the ethanol-treated proactive individuals showed lower stress-related behaviors than their reactive counterparts. Proactive individuals showed significantly higher expression of gabra1, GABRA2, and gabrg2 compared to reactive individuals and ethanol treatment resulted in upregulation of gabra1 and gabrg2 in both stress coping styles. These results show that differences in stress-related behaviors between stress coping styles may be facilitated in part by expression of select GABAA receptor subunits.
Robert A. Zucker - One of the best experts on this subject based on the ideXlab platform.
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Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.
Journal of abnormal psychology, 2016Co-Authors: Elisa M. Trucco, Brian M. Hicks, Sandra Villafuerte, Joel T. Nigg, Margit Burmeister, Robert A. ZuckerAbstract:Understanding how specific genes contribute to risk for addiction remains challenging. This study tests whether childhood temperament and externalizing behavior in early adolescence account for a portion of the association between specific genetic variants and substance use problems in late adolescence. The sample consisted of 487 adolescents from the Michigan Longitudinal Study, a high-risk sample (70.2% male, 81.7% European American ancestry). Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems. The temperament traits behavioral control and resiliency were assessed using interviewer ratings (ages 9-11), and externalizing behavior (ages 12-14) was assessed using teacher ratings. Self-reported substance use outcomes (ages 15-17) included maximum alcoholic beverages consumed in 24 hours, and frequency of past year cigarette and marijuana use. Behavioral control, resiliency, and externalizing behavior accounted for the associations between polymorphisms in noradrenergic and GABAergic genes and substance use in late adolescence. Individual differences in emotional coping and behavioral regulation represent nonspecific neurobiological underpinnings for an externalizing pathway to addiction. (PsycINFO Database Record
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Susceptibility effects of GABA receptor subunit alpha-2 (GABRA2) variants and parental monitoring on externalizing behavior trajectories: Risk and protection conveyed by the minor allele.
Development and psychopathology, 2015Co-Authors: Elisa M. Trucco, Sandra Villafuerte, Margit Burmeister, Mary M. Heitzeg, Robert A. ZuckerAbstract:Understanding factors increasing susceptibility to social contexts and predicting psychopathology can help identify targets for prevention. Persistently high externalizing behavior in adolescence is predictive of psychopathology in adulthood. Parental monitoring predicts low externalizing behavior, yet youth likely vary in the degree to which they are affected by parents. Genetic variants of GABA receptor subunit alpha-2 (GABRA2) may increase susceptibility to parental monitoring, thus impacting externalizing trajectories. We had several objectives: (a) to determine whether GABRA2 (rs279827, rs279826, rs279858) moderates the relationship between a component of parental monitoring, parental knowledge, and externalizing trajectories; (b) to test the form of this interaction to assess whether GABRA2 variants reflect risk (diathesis-stress) or susceptibility (differential susceptibility) factors; and (c) to clarify GABRA2 associations on the development of problem behavior. This prospective study (N = 504) identified three externalizing trajectory classes (i.e., low, decreasing, and high) across adolescence. A GABRA2 × Parental Monitoring effect on class membership was observed, such that A-carriers were largely unaffected by parental monitoring, whereas class membership for those with the GG genotype was affected by parental monitoring. Findings support differential susceptibility in GABRA2.
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Rule breaking mediates the developmental association between GABRA2 and adolescent substance abuse.
Journal of child psychology and psychiatry and allied disciplines, 2014Co-Authors: Elisa M. Trucco, Sandra Villafuerte, Margit Burmeister, Mary M. Heitzeg, Robert A. ZuckerAbstract:Background: This study’s primary aim was to examine age-specific associations between GABRA2, rule breaking, problematic alcohol use, and substance abuse symptomatology. The secondary aim was to examine the extent to which rule breaking mediates the GABRA2-substance abuse relationship. Methods: A sample (n = 518) of primarily male (70.9%) and White (88.8%) adolescents from the Michigan Longitudinal Study was assessed from ages 11–18. Age-specific effects of GABRA2 on rule breaking, problematic alcohol use, and substance abuse symptomatology were examined using nested path models. The role of rule breaking as a mediator in the association between GABRA2 and substance abuse outcomes was tested using prospective cross-lagged path models. Results: GABRA2 is significantly (p < 0.05) associated with rule breaking in mid- to late-adolescence, but not substance abuse symptomatology across adolescence. GABRA2 effects on problematic alcohol use and substance abuse symptomatology operate largely (45.3% and 71.1%, respectively, p < 0.05) via rule breaking in midadolescence. Conclusions: GABRA2 represents an early risk factor for an externalizing pathway to the development of problematic alcohol and drug use. Keywords: GABRA2, rule breaking, substance abuse, adolescence, mediation.
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Impulsiveness mediates the association between GABRA2 SNPs and lifetime alcohol problems
Genes brain and behavior, 2013Co-Authors: Sandra Villafuerte, Robert A. Zucker, Viktorya Strumba, Scott F. Stoltenberg, Margit BurmeisterAbstract:Genetic variants in GABRA2 have previously been shown to be associated with alcohol measures, electroencephalography (EEG) β waves and impulsiveness-related traits. Impulsiveness is a behavioral risk factor for alcohol and other substance abuse. Here, we tested association between 11 variants in GABRA2 with NEO-impulsiveness and problem drinking. Our sample of 295 unrelated adult subjects was from a community of families with at least one male with DSM-IV alcohol use diagnosis, and from a socioeconomically comparable control group. Ten GABRA2 SNPs (single-nucleotide polymorphisms) were associated with the NEO-impulsiveness (P
Alexander C. Goodman - One of the best experts on this subject based on the ideXlab platform.
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Differential effects of ethanol on behavior and GABAA receptor expression in adult zebrafish (Danio rerio) with alternative stress coping styles.
Scientific reports, 2020Co-Authors: Alexander C. Goodman, Ryan Y. WongAbstract:Variation in stress responses between individuals are linked to factors ranging from stress coping styles to sensitivity of neurotransmitter systems. Many anxiolytic compounds (e.g. ethanol) can increase stressor engagement through modulation of neurotransmitter systems and are used to investigate stress response mechanisms. There are two alternative suites of correlated behavioral and physiological responses to stressors (stress coping styles) that differ in exploration tendencies: proactive and reactive stress coping styles. By chronically treating individuals differing in stress coping style with ethanol, a GABA-acting drug, we assessed the role of the GABAergic system on the behavioral stress response. Specifically, we investigated resulting changes in stress-related behavior (i.e. exploratory behavior) and whole-brain GABAA receptor subunits (gabra1, GABRA2, gabrd, & gabrg2) in response to a novelty stressor. We found that ethanol-treated proactive individuals showed lower stress-related behaviors than their reactive counterparts. Proactive individuals showed significantly higher expression of gabra1, GABRA2, and gabrg2 compared to reactive individuals and ethanol treatment resulted in upregulation of gabra1 and gabrg2 in both stress coping styles. These results suggest that impacts of ethanol on stress-related behaviors vary by stress coping style and that expression of select GABAA receptor subunits may be one of the underlying mechanisms.
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Differential effects of ethanol on behavior and GABAA receptor subunit expression in zebrafish (Danio rerio) with alternative stress coping styles
2019Co-Authors: Alexander C. Goodman, Ryan Y. WongAbstract:Variation in stress responses between individuals is linked to factors ranging from stress coping styles to sensitivity of neurotransmitter systems. Many anxiolytic compounds (e.g. ethanol) can increase stressor engagement through modulation of neurotransmitter systems and are used to investigate stress response mechanisms. Here we assessed the role of the GABAA system on the variation of the behavioral stress response by comparing individuals differing in stress coping styles that were chronically treated with ethanol. Specifically, we investigated resulting changes in stress-related behavior and whole-brain GABAA receptor subunits (gabra1, GABRA2, gabrd, & gabrg2) in response to a novelty stressor. There were significant main and interaction effects on two stress-related behaviors, where the ethanol-treated proactive individuals showed lower stress-related behaviors than their reactive counterparts. Proactive individuals showed significantly higher expression of gabra1, GABRA2, and gabrg2 compared to reactive individuals and ethanol treatment resulted in upregulation of gabra1 and gabrg2 in both stress coping styles. These results show that differences in stress-related behaviors between stress coping styles may be facilitated in part by expression of select GABAA receptor subunits.
Margit Burmeister - One of the best experts on this subject based on the ideXlab platform.
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Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.
Journal of abnormal psychology, 2016Co-Authors: Elisa M. Trucco, Brian M. Hicks, Sandra Villafuerte, Joel T. Nigg, Margit Burmeister, Robert A. ZuckerAbstract:Understanding how specific genes contribute to risk for addiction remains challenging. This study tests whether childhood temperament and externalizing behavior in early adolescence account for a portion of the association between specific genetic variants and substance use problems in late adolescence. The sample consisted of 487 adolescents from the Michigan Longitudinal Study, a high-risk sample (70.2% male, 81.7% European American ancestry). Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems. The temperament traits behavioral control and resiliency were assessed using interviewer ratings (ages 9-11), and externalizing behavior (ages 12-14) was assessed using teacher ratings. Self-reported substance use outcomes (ages 15-17) included maximum alcoholic beverages consumed in 24 hours, and frequency of past year cigarette and marijuana use. Behavioral control, resiliency, and externalizing behavior accounted for the associations between polymorphisms in noradrenergic and GABAergic genes and substance use in late adolescence. Individual differences in emotional coping and behavioral regulation represent nonspecific neurobiological underpinnings for an externalizing pathway to addiction. (PsycINFO Database Record
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Susceptibility effects of GABA receptor subunit alpha-2 (GABRA2) variants and parental monitoring on externalizing behavior trajectories: Risk and protection conveyed by the minor allele.
Development and psychopathology, 2015Co-Authors: Elisa M. Trucco, Sandra Villafuerte, Margit Burmeister, Mary M. Heitzeg, Robert A. ZuckerAbstract:Understanding factors increasing susceptibility to social contexts and predicting psychopathology can help identify targets for prevention. Persistently high externalizing behavior in adolescence is predictive of psychopathology in adulthood. Parental monitoring predicts low externalizing behavior, yet youth likely vary in the degree to which they are affected by parents. Genetic variants of GABA receptor subunit alpha-2 (GABRA2) may increase susceptibility to parental monitoring, thus impacting externalizing trajectories. We had several objectives: (a) to determine whether GABRA2 (rs279827, rs279826, rs279858) moderates the relationship between a component of parental monitoring, parental knowledge, and externalizing trajectories; (b) to test the form of this interaction to assess whether GABRA2 variants reflect risk (diathesis-stress) or susceptibility (differential susceptibility) factors; and (c) to clarify GABRA2 associations on the development of problem behavior. This prospective study (N = 504) identified three externalizing trajectory classes (i.e., low, decreasing, and high) across adolescence. A GABRA2 × Parental Monitoring effect on class membership was observed, such that A-carriers were largely unaffected by parental monitoring, whereas class membership for those with the GG genotype was affected by parental monitoring. Findings support differential susceptibility in GABRA2.
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Rule breaking mediates the developmental association between GABRA2 and adolescent substance abuse.
Journal of child psychology and psychiatry and allied disciplines, 2014Co-Authors: Elisa M. Trucco, Sandra Villafuerte, Margit Burmeister, Mary M. Heitzeg, Robert A. ZuckerAbstract:Background: This study’s primary aim was to examine age-specific associations between GABRA2, rule breaking, problematic alcohol use, and substance abuse symptomatology. The secondary aim was to examine the extent to which rule breaking mediates the GABRA2-substance abuse relationship. Methods: A sample (n = 518) of primarily male (70.9%) and White (88.8%) adolescents from the Michigan Longitudinal Study was assessed from ages 11–18. Age-specific effects of GABRA2 on rule breaking, problematic alcohol use, and substance abuse symptomatology were examined using nested path models. The role of rule breaking as a mediator in the association between GABRA2 and substance abuse outcomes was tested using prospective cross-lagged path models. Results: GABRA2 is significantly (p < 0.05) associated with rule breaking in mid- to late-adolescence, but not substance abuse symptomatology across adolescence. GABRA2 effects on problematic alcohol use and substance abuse symptomatology operate largely (45.3% and 71.1%, respectively, p < 0.05) via rule breaking in midadolescence. Conclusions: GABRA2 represents an early risk factor for an externalizing pathway to the development of problematic alcohol and drug use. Keywords: GABRA2, rule breaking, substance abuse, adolescence, mediation.
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Impulsiveness mediates the association between GABRA2 SNPs and lifetime alcohol problems
Genes brain and behavior, 2013Co-Authors: Sandra Villafuerte, Robert A. Zucker, Viktorya Strumba, Scott F. Stoltenberg, Margit BurmeisterAbstract:Genetic variants in GABRA2 have previously been shown to be associated with alcohol measures, electroencephalography (EEG) β waves and impulsiveness-related traits. Impulsiveness is a behavioral risk factor for alcohol and other substance abuse. Here, we tested association between 11 variants in GABRA2 with NEO-impulsiveness and problem drinking. Our sample of 295 unrelated adult subjects was from a community of families with at least one male with DSM-IV alcohol use diagnosis, and from a socioeconomically comparable control group. Ten GABRA2 SNPs (single-nucleotide polymorphisms) were associated with the NEO-impulsiveness (P
Berta Maria Heinzmann - One of the best experts on this subject based on the ideXlab platform.
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GABAa receptor subunits expression in silver catfish (Rhamdia quelen) brain and its modulation by Nectandra grandiflora Nees essential oil and isolated compounds.
Behavioural brain research, 2019Co-Authors: Quelen Iane Garlet, Carine F. Souza, Patricia Rodrigues, Sharine N. Descovi, Gonzalo Martínez-rodríguez, Bernardo Baldisserotto, Berta Maria HeinzmannAbstract:Studies using silver catfish (Rhamdia quelen) as experimental models are often applied to screen essential oils (EO) with GABAergic-mediated effects. However, the expression of GABAa receptors in the silver catfish brain remains unknown. Thus, we assessed whether silver catfish express GABAa receptor subunits associated with sedation/anesthetic process and/or neurological diseases. Additionally, we evaluated the brain expression of GABAa receptor subunits in fish sedated with Nectandra grandiflora EO and its isolated compounds, the fish anesthetic (+)-dehydrofukinone (DHF), and dehydrofukinone epoxide (DFX), eremophil-11-en-10-ol (ERM) and selin-11-en-4-α-ol (SEL), which have GABAa-mediated anxiolytic-like effects in mice. The expression of the subunits gabra1, GABRA2, gabra3, gabrb1, gabrd and gabrg2 in the silver catfish brain were assessed after a 24h-sedation bath by real time PCR. Since qPCR data rarely describes mechanisms of action, which are usually found through interactions with receptors, we also performed an antagonist-driven experiment using flumazenil (FMZ). Real-time PCR detected the mRNA expression of all targeted genes in R. quelen brain. The expression of gabra1 was decreased in fish sedated with ERM; EO increased GABRA2, gabra3, gabrb1 and gabrg2 expression; SEL increased gabrb1, gabrd and gabrg2 expression. EO and compounds DFX, SEL and ERM induced sustained sedation in fish and FMZ-bath prompted the recovery from ERM- and DFX-induced sedation. Our results suggest that the EO, SEL, ERM and DFX sedative effects involve interaction with the GABAergic system. Our findings support the use of the silver catfish as robust and reliable experimental model to evaluate the efficacy of drugs with putative GABAergic-mediated effects.