Opioid pharmacogenetics of alcohol addiction

Berrettini, Wade H.

doi:10.1093/acprof:oso/9780199655786.003.0011

Cited by 3 publications

(3 citation statements)

References 28 publications

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“…take effect through β-endorphin neurotransmitters activating the µ and δ opium receptors [71] . Alcohol takes effect through promoting the reaction of the GABAA receptor [72] and increasing stimulation to the dopamine and opiate receptor [73] , [74] . Nicotine takes effect through acetylcholine neurotransmitters activating the α2β4nACh receptor [75] – [77] .…”

Section: Discussionmentioning

confidence: 99%

Impact of Physical Exercise on Substance Use Disorders: A Meta-Analysis

et al. 2014

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ObjectiveThe goal of this meta-analysis was to examine whether long-term physical exercise could be a potential effective treatment for substance use disorders (SUD).MethodsThe PubMed, Web of Science, Elsevier, CNKI and China Info were searched for randomized controlled trials (RCT) studies in regards to the effects of physical exercise on SUD between the years 1990 and 2013. Four main outcome measures including abstinence rate, withdrawal symptoms, anxiety, and depression were evaluated.ResultsTwenty-two studies were integrated in the meta-analysis. The results indicated that physical exercise can effectively increase the abstinence rate (OR = 1.69 (95% CI: 1.44, 1.99), z = 6.33, p<0.001), ease withdrawal symptoms (SMD = −1.24 (95% CI: −2.46, −0.02), z = −2, p<0.05), and reduce anxiety (SMD = −0.31 (95% CI: −0.45, −0.16), z = −4.12, p<0.001) and depression (SMD = −0.47 (95% CI: −0.80, −0.14), z = −2.76, p<0.01). The physical exercise can more ease the depression symptoms on alcohol and illicit drug abusers than nicotine abusers, and more improve the abstinence rate on illicit drug abusers than the others. Similar treatment effects were found in three categories: exercise intensity, types of exercise, and follow-up periods.ConclusionsThe moderate and high-intensity aerobic exercises, designed according to the Guidelines of American College of Sports Medicine, and the mind-body exercises can be an effective and persistent treatment for those with SUD.

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Section: Discussionmentioning

confidence: 99%

Impact of Physical Exercise on Substance Use Disorders: A Meta-Analysis

et al. 2014

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“…Given the well-documented interactions between alcohol and the opioid system (Arias & Kranzler, 2008; Berrettini, 2013; Gianoulakis, 2001; Gianoulakis et al, 1989; Job et al, 2007; Oslin, Berrettini, & O’Brien, 2006), we next wanted to assess alcohol use risk in offspring maternally exposed to morphine. The offspring tested in the battery of behavioral tests during adolescence were allowed to mature into adulthood and were then evaluated in an ethanol intermittent two-bottle choice (I2BC) paradigm (Figure 6a), which has been used to assess voluntary ethanol intake (Carnicella et al, 2014; Hwa et al, 2011; Quijano Cardé & De Biasi, 2022; Quijano Cardé et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

In utero exposure to morphine leads to sex-specific behavioral alterations that persist into adulthood in cross-fostered mice

Fleites

Markwalter²,

Johnson³

et al. 2022

Preprint

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Introduction: The opioid epidemic has seen an increase in drug use among women of reproductive age. It is well established that Opioid Use Disorder (OUD) can have many negative consequences for the health of mothers and their babies, both during pregnancy and after delivery, but our understanding of the impact of fetal opioid exposure on behavior during adolescence and adulthood is less understood. Preclinical studies have unveiled some of the long-term effects of in utero morphine exposure primarily using injections as the route of drug delivery. Our study utilized a model for oral, voluntary morphine self-administration to investigate neonate, adolescent, and adult offspring behavioral phenotypes and subsequent ethanol misuse liability. Methods: We first validated a paradigm for maternal oral intake of morphine, where female mice became morphine dependent pre-pregnancy, and continued to voluntarily consume morphine in the continuous two-bottle choice (C2BC) paradigm during pregnancy and up to offspring postnatal day 7 (PND 7). Offspring were cross-fostered to a drug-naive dam at PND 7, to model first and second trimester in utero exposure in humans and to mimic the stress associated with NOWS. Bodyweight and ultrasonic vocalizations were assessed to determine alterations in the neonates. Offspring from control and morphine-exposed dams were then tested during adolescence and adulthood in a battery of behavioral tests to assess baseline behavioral phenotypes. We also computed a global behavioral score (GBS) to integrate offspring multiple behavioral outcomes into a composite score that could be used to identify potential vulnerable and resilient populations in offspring exposed prenatally to morphine. Offspring that were tested during adolescence were also evaluated during adulthood in the ethanol intermittent 2BC to assess ethanol misuse risk. Results: Using an oral maternal morphine C2BC protocol, we demonstrated that morphine dams display signs of dependence, measured by somatic signs during withdrawal, and voluntarily drink morphine throughout gestation. Neonate cross-fostered offspring display changes in spontaneous activity, body weight, and ultrasonic vocalization parameters. During adolescence, offspring display both increased baseline anxiety-like/compulsive-like behavior, while in adulthood they display increased anxiety-like behavior. No changes were found for baseline physical signs, locomotion, and depressive-like behavior during adolescence or adulthood. In addition, a greater percentage of adult male offspring exposed to maternal morphine fell into moderate and high GBS classifications, signaling a more severe behavioral phenotype, compared to male control offspring. These effects were not observed in adult female offspring exposed to morphine in utero. Additionally, male adult offspring exposed to maternal morphine reduced their 2-hour ethanol intake in the intermittent two-bottle choice (I2BC) paradigm, although no changes in 24-hour ethanol intake and preference were found. No changes were observed in female offspring of morphine-exposed dams. Conclusion: Overall, maternal morphine exposure leads to sex-specific changes in neonate, adolescent, and adult behavior, including ethanol intake.

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“…In fact, the most prominent SNPs that have been linked to alcohol abuse, identified using genome wide association studies (GWAS), have been mapped to genes encoding liver enzymes, specifically alcohol dehydrogenase and aldehyde dehydrogenase (Tawa, Hall, & Lohoff, 2016). However, there are also a number of studies implicating genes that modulate synaptic function such as OPRM1, CHRNA5 and GABRA2 to alcohol abuse as well, suggesting that AUDs have a key neuropsychiatric component that has not been thoroughly investigated (Berrettini, 2013;Hoehe et al, 2000;D. Li et al, 2014;Lubke, Stephens, Lessem, Hewitt, & Ehringer, 2012).…”

Section: Current Work Attempting To Use Ips Cell Technology To Model mentioning

confidence: 99%

Using human stem cells as a model system to understand the neural mechanisms of alcohol use disorders: Current status and outlook

Scarnati

Halikere

Pang

2019

Alcohol

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Alcohol use disorders (AUDs), which include alcohol abuse and dependence, are among the most common types of neuropsychiatric disorders in the United States (U.S.). Approximately 14% of the U.S. population is affected in a single year, thus placing a tremendous burden on individuals from all socioeconomic backgrounds. Animal models have been pivotal in revealing the basic mechanisms of how alcohol impacts neuronal function, yet there are currently limited effective therapies developed based on these studies. This is mainly due to a limited understanding of the exact cellular and molecular mechanisms underlying AUDs in humans, which leads to a lack of targeted therapeutics. Furthermore, compounding factors including genetic background, gene copy number variants, single nucleotide polymorphisms (SNP) as well as environmental and social factors that affect and promote the development of AUDs are complex and heterogeneous. Recent developments in stem cell biology, especially the human induced pluripotent stem (iPS) cell development and differentiation technologies, has provided us a unique opportunity to model neuropsychiatric disorders like AUDs in a manner that is highly complementary to animal studies, but that maintains fidelity with complex human genetic contexts. Patient-specific neuronal cells derived from iPS cells can then be used for drug discovery and precision medicine, e.g. for pathway-directed development in alcoholism. Here, we review recent work employing iPS cell technology to model and elucidate the genetic, molecular and cellular mechanisms of AUDs in a human neuronal background and provide our perspective on future development in this direction.

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Opioid pharmacogenetics of alcohol addiction

Cited by 3 publications

References 28 publications

Impact of Physical Exercise on Substance Use Disorders: A Meta-Analysis

Impact of Physical Exercise on Substance Use Disorders: A Meta-Analysis

In utero exposure to morphine leads to sex-specific behavioral alterations that persist into adulthood in cross-fostered mice

Using human stem cells as a model system to understand the neural mechanisms of alcohol use disorders: Current status and outlook

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