Maintaining abstinence from alcohol with γ-hydroxybutyric acid

Addolorato, Giovanni; Cibin, Mauro; Caprista, Esmeralda; Beghè, F.; Gessa, G L; Stefanini, Giuseppe Francesco; Gasbarrini, Giovanni

doi:10.1016/s0140-6736(05)78088-0

Cited by 53 publications

(27 citation statements)

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“…␥-Hydroxybutyric acid (GHB), a GABA metabolite naturally present in the brain that in pharmacological doses modulates a variety of neurotransmission systems (Gessa et al, 1968;Bernasconi et al, 1999), has also been proposed for use in the treatment of persons with this condition (Gallimberti et al, 1992;Addolorato et al, 1998). Although specific recognition sites for GHB have been identified in the brain (Benavides et al, 1982), it remains unclear whether all the effects of this compound are mediated by these sites.…”

mentioning

confidence: 99%

γ-Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABA_A Receptors α₄ Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells

Follesa

Mancuso²,

Biggio³

et al. 2003

Mol Pharmacol

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Both benzodiazepines and ␥-hydroxybutyric acid (GHB) are used to treat alcohol withdrawal syndrome. The molecular basis for this therapeutic efficacy was investigated with primary cultures of rat cerebellar granule cells. Long-term exposure of these cells to ethanol (100 mM, 5 days) reduced the abundance of mRNAs encoding the ␥ 2 L and ␥ 2 S subunits of the GABA type A receptor (Ϫ32 and Ϫ23%, respectively) but failed to affect that of ␣ 1 , ␣ 4 , or ␣ 6 subunit mRNAs. Subsequent ethanol withdrawal resulted in decreases in the amounts of ␣ 1 (Ϫ29%), ␣ 6 (Ϫ27%), ␥ 2 L (Ϫ64%), and ␥ 2 S (Ϫ76%),subunit mRNAs that were maximal after 6 to 12 h. In contrast, 3 h after ethanol withdrawal, the abundance of the ␣ 4 subunit mRNA was increased by 46%. Ethanol withdrawal did not affect neuronal morphology but reduced cellular metabolic activity. The increase in ␣ 4 subunit was confirmed by functional studies showing a positive action of flumazenil in patch clamp recordings of GABA-stimulated currents after ethanol withdrawal. Diazepam (10 M) or GHB (100 mM) prevented the increase in the amount of the ␣ 4 subunit mRNA, the metabolic impairment, and the positive action of flumazenil induced by ethanol withdrawal but failed to restore the expression of the ␣ 1 and ␥ 2 subunits. The antagonism by GHB seems not to be mediated by a direct action at GABA A R because GHB failed to potentiate the effects of GABA or diazepam on Cl Ϫ currents mediated by GABA type A receptor.

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mentioning

confidence: 99%

γ-Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABA_A Receptors α₄ Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells

Follesa

Mancuso²,

Biggio³

et al. 2003

Mol Pharmacol

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“…A large multicenter trial with a parenteral application of bromocriptine showed that this substance did not reduce relapse rates [41]. GHB was effective in reducing relapses [2,3,13,19]. In a randomized, double-blind, double-dummy study, performed in our center, 50 mg/kg GHB reduced craving during withdrawal effectively.…”

Section: Da Agonists For Relapse Preventionmentioning

confidence: 93%

Dopamine and Alcohol Relapse: D<sub>1</sub> and D<sub>2</sub> Antagonists Increase Relapse Rates in Animal Studies and in Clinical Trials

Walter¹,

Ramskogler²,

Semler³

et al. 2001

Journal of Biomedical Science

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A considerable number of animal studies on the effects of dopaminergic agents on alcohol intake behavior have been performed. Acute alcohol administration in rats induces dopamine release in the caudate nucleus and in the nucleus accumbens, an effect related among others to reinforcement. It has been repeatedly suggested that D₁ and D₂ receptor activation mediates reward. As alcohol consumption and dopaminergic transmission seem to have a close relationship, all kinds of dopaminergic agents may be regarded as putative therapeutics for preventing relapse. In a prospective European double-blind multicenter clinical trial, comparing the D₁, D₂, D₃ antagonist flupenthixol and placebo in 281 chronic alcohol-dependent patients (27.4% women), the application of the Lesch typology made an outcome differentiation possible. It could be shown in which patients flupenthixol administration was followed by a significantly higher relapse rate and in which patient groups no differences were found when compared to placebo.

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“…5HT1A parsiyel agonisti olan buspiron ve 5HT2 reseptör antagonisti ritanserininin ise plasebodan farksız olduğu bildirilmiştir (33,43,49). Bir endojen nöro düzen-leyici olan GHB'nin alkol yoksunluk belirtilerini ve aşer-meyi azalttığı öne sürülmüştür (50). Bir yandan da kannabinoid antagonistleri, kortikotiropin serbestleştirici faktör antagonistleri, nöropeptid Y ve immünoterapiler üzerine çalışmalar devam etmektedir (51).…”

Section: Alkol Aşermesinin Tedavisiunclassified

Neurobiology, genetics and treatment of alcohol craving

Şengül¹,

Dılbaz²

2013

Dusunen Adam

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Derleme / Review ÖZET Alkol aşermesinin nörobiyolojisi, genetiği ve tedavisiAlkol aşermesi son 10 yılda, giderek artan bir şekilde, alkol kullanım bozukluklarında önemli bir sorun olarak kabul edilmektedir. Alkol aşermesi ile ilgili yapılan biyolojik çalışmalar, daha çok nörobiyoloji, genetik ve bu durumun farmakolojik tedavisi üzerine odaklanmaktadır. Biz bu yazımızda, reseptör sistemlerinden başlayarak, alkol aşermesinin genetiği ve epigenetiğini gözden geçirdik. Son olarak da, alkol aşermesinde kullanılan ana ilaçlardan başlayarak, alkol aşermesinde kullanılması muhtemel diğer ilaçları ve gelecekteki olası tedavi seçeneklerini açıklamaya çalıştık.Anahtar kelimeler: Alkol aşermesi, genetik, nörobiyoloji, tedavi ABSTRACT Neurobiology, genetics and treatment of alcohol craving Alcohol craving has increasingly been considered an important issue in alcohol use disorders in the last decade. Biologic studies on alcohol craving were mainly focused on neurobiology, genetics and pharmacological treatment of this condition. In this report, we started from receptor systems, than we explained genetics and epigenetics of alcohol craving. At last, we described the main drugs currently used in the treatment of alcohol craving. Other potential drugs and future choices for treating alcohol craving were also described. GİRİŞA lkol aşermesi (alcohol craving), alkol almaya karşı kontrol edilemeyen bir arzu ve bu arzunun tatmin edilememesi durumunda ortaya çıkan anksiyete, asteni, anoreksi, insomnia gibi belirtileri içermektedir (1). Oxford sözlüğünde, "a strong desire" (çok güçlü bir istek) olarak tanımlanan "craving" kavramı için Türkçede istek, arzu ve aşerme gibi karşılıklar kullanılmakta olup, biz, yazımızda daha uygun olduğunu düşündüğümüz "aşerme" karşılığını kullandık. Kişi alkol kullanmaya başlayınca, öncelikle alkol kullanmaya karşı çok güçlü bir istek gelişmekte ve bu istek uzun bir süre boyunca varlığını ve etkisini sürdürmektedir. Sonuçta, ciddi yan etkilerine ve önemli olumsuz sonuçlarına rağmen kişi alkolü kullanmaya devam etmektedir (1,2).Beyin ödül sistemi, maddenin pekiştirici etkisi ve aşerme bağımlılık nörobiyolojisinin 3 temel saç ayağını oluşturmaktadır (3). Öncelikle, bir maddenin bağımlılık yapması için haz verici etkisinin olması zorunludur. Bu sebeple, bağımlılık eşittir beyin ödül sistemi hipotezi ortaya atılmış ve bu görüşün ispatına çalışılmıştır. Yapılan araştırmalarda, gerçekten de nükleus akumbensin ve nörotransmiter olarak dopaminin bağımlılık gelişimindeki rolü gösterilmiş, ama bağımlılık ile ilgili tüm süreçleri açıklamada bu hipotez yetersiz kalmıştır (4). Sonrasında, bağımlılık gelişiminde tek nedenin ödüllendirme olamayacağı, zira bağımlı olmayan insanların da madde kullandıklarında bundan aynı derecede keyif aldıkları saptanmış ve bu bağlamda, bağımlılıkta ödüllendirme dışı süreçlerin üzerinde durulmasının gerekliliği hususunda giderek daha fazla vurgu yapıl-maya başlanmıştır. Aşerme kavramı bu süreçte devreye girmiş ve öncelikle yoksunluğun bir belirtisi olarak ele alınmış, daha sonraki yıl...

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Maintaining abstinence from alcohol with γ-hydroxybutyric acid

Cited by 53 publications

References 5 publications

γ-Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABA_A Receptors α₄ Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells

γ-Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABA_A Receptors α₄ Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells

Dopamine and Alcohol Relapse: D<sub>1</sub> and D<sub>2</sub> Antagonists Increase Relapse Rates in Animal Studies and in Clinical Trials

Neurobiology, genetics and treatment of alcohol craving

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Maintaining abstinence from alcohol with γ-hydroxybutyric acid

Cited by 53 publications

References 5 publications

γ-Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABAA Receptors α4 Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells

γ-Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABAA Receptors α4 Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells

Dopamine and Alcohol Relapse: D<sub>1</sub> and D<sub>2</sub> Antagonists Increase Relapse Rates in Animal Studies and in Clinical Trials

Neurobiology, genetics and treatment of alcohol craving

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γ-Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABA_A Receptors α₄ Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells

γ-Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABA_A Receptors α₄ Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells