Genetic studies of alcohol dependence in the context of the addiction cycle.


:Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of alcohol use disorders is estimated at approximately 50-60% of the total phenotypic variability. Vulnerability to alcohol use disorders can be due to multiple genetic or environmental factors or their interaction which gives rise to extensive and daunting heterogeneity. This heterogeneity makes it a significant challenge in mapping and identifying the specific genes that influence alcohol use disorders. Genetic linkage and (candidate gene) association studies have been used now for decades to map and characterize genomic loci and genes that underlie the genetic vulnerability to alcohol use disorders. These approaches have been moderately successful in identifying several genes that contribute to the complexity of alcohol use disorders. Recently, genome-wide association studies have become one of the major tools for identifying genes for alcohol use disorders by examining correlations between millions of common single-nucleotide polymorphisms with diagnosis status. Genome-wide association studies are just beginning to uncover novel biology; however, the functional significance of results remains a matter of extensive debate and uncertainty. In this review, we present a select group of genome-wide association studies of alcohol dependence, as one example of a way to generate functional hypotheses, within the addiction cycle framework. This analysis may provide novel directions for validating the functional significance of alcohol dependence candidate genes. This article is part of the Special Issue entitled "Alcoholism".






Reilly MT,Noronha A,Goldman D,Koob GF




Has Abstract


2017-08-01 00:00:00












  • Pharmacological characterization of synaptic transmission through mGluRs in rat cerebellar slices.

    abstract::The mGluR-mediated EPSP at parallel fibre-Purkinje cell synapses in the cerebellum was blocked concentration-dependently and reversibly by antagonists acting selectively on group-I mGluRs but not by an inhibitor of group-III receptors. The results provide pharmacological evidence that the receptor type responsible for...


    pub_type: 杂志文章


    authors: Batchelor AM,Knöpfel T,Gasparini F,Garthwaite J

    更新日期:1997-03-01 00:00:00

  • Vaccine blunts fentanyl potency in male rhesus monkeys.

    abstract::One proposed factor contributing to the increased frequency of opioid overdose deaths is the emergence of novel synthetic opioids, including illicit fentanyl and fentanyl analogues. A treatment strategy currently under development to address the ongoing opioid crisis is immunopharmacotherapies or opioid-targeted vacci...


    pub_type: 杂志文章


    authors: Tenney RD,Blake S,Bremer PT,Zhou B,Hwang CS,Poklis JL,Janda KD,Banks ML

    更新日期:2019-11-01 00:00:00

  • Mefloquine in the nucleus accumbens promotes social avoidance and anxiety-like behavior in mice.

    abstract::Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperito...


    pub_type: 杂志文章


    authors: Heshmati M,Golden SA,Pfau ML,Christoffel DJ,Seeley EL,Cahill ME,Khibnik LA,Russo SJ

    更新日期:2016-02-01 00:00:00

  • Depression of the monosynaptic reflex by apomorphine or bromocriptine is not mediated by D1/D2 receptors.

    abstract::The role of dopamine in spinal motor transmission was investigated using spinal reflexes in acutely spinalized rats. Intravenous administration of a relatively high dose of the dopamine receptor agonist apomorphine-HCl (3 mg/kg) or the D2 receptor agonist bromocriptine mesylate (1 mg/kg) reduced the amplitude of the m...


    pub_type: 杂志文章


    authors: Kamijo N,Nagao T,Ono H

    更新日期:1993-08-01 00:00:00

  • GABA(B) receptor activation inhibits dopamine D1 receptor-mediated facilitation of [(3)H]GABA release in substantia nigra pars reticulata.

    abstract::GABA(B) receptors inhibit and dopamine D1 receptors stimulate the release of GABA from striatal terminals in the pars reticulata of the substantia nigra. Here we have studied the interaction between both classes of receptors by exploring the effect of GABA(B) receptors upon the stimulation of depolarization-induced [(...


    pub_type: 杂志文章


    authors: Nava-Asbell C,Paz-Bermudez F,Erlij D,Aceves J,Florán B

    更新日期:2007-10-01 00:00:00

  • Olvanil: a non-pungent TRPV1 activator has anti-emetic properties in the ferret.

    abstract::Anti-emetic drugs such as the tachykinin NK(1) receptor antagonists are useful to control emesis induced by diverse challenges. Evidence suggests pungent capsaicin-like TRPV1 activators also have broad inhibitory anti-emetic activity. However, pungent compounds are associated with undesirable effects including adverse...


    pub_type: 杂志文章


    authors: Chu KM,Ngan MP,Wai MK,Yeung CK,Andrews PL,Percie du Sert N,Rudd JA

    更新日期:2010-02-01 00:00:00

  • Neuron-specific chromatin remodeling: a missing link in epigenetic mechanisms underlying synaptic plasticity, memory, and intellectual disability disorders.

    abstract::Long-term memory formation requires the coordinated regulation of gene expression. Until recently nucleosome remodeling, one of the major epigenetic mechanisms for controlling gene expression, had been largely unexplored in the field of neuroscience. Nucleosome remodeling is carried out by chromatin remodeling complex...


    pub_type: 杂志文章,评审


    authors: Vogel-Ciernia A,Wood MA

    更新日期:2014-05-01 00:00:00

  • Methionine 286 in transmembrane domain 3 of the GABAA receptor beta subunit controls a binding cavity for propofol and other alkylphenol general anesthetics.

    abstract::gamma-Aminobutyric acid type A (GABA(A)) receptors are an important target for general anesthetics in the central nervous system. Site-directed mutagenesis techniques have identified amino acid residues that are important for the positive modulation of GABA(A) receptors by general anesthetics. In the present study, we...


    pub_type: 杂志文章


    authors: Krasowski MD,Nishikawa K,Nikolaeva N,Lin A,Harrison NL

    更新日期:2001-12-01 00:00:00

  • The actions of (-)N-n-propylnorapomorphine and selective dopamine D1 and D2 receptor agonists to modify the release of [3H]dopamine from the rat nucleus accumbens.

    abstract::The ability of (-)N-n-propylnorapomorphine and selective D1 and D2 dopamine receptor agonists and antagonists to modify the release of [3H]dopamine, induced by potassium from the nucleus accumbens, was studied using an in vitro superfusion technique. (-)N-n-Propylnorapomorphine, in picomolar concentrations, inhibited ...


    pub_type: 杂志文章


    authors: Barnes JM,Barnes NM,Costall B,Naylor RJ

    更新日期:1990-04-01 00:00:00

  • High affinity, heterogeneous displacement of [3H]EBOB binding to cerebellar GABA A receptors by neurosteroids and GABA agonists.

    abstract::Heterogeneous binding interactions of cerebellar GABA(A) receptors were investigated with GABA agonists and neurosteroids. GABA(A) receptors of rat cerebellum were labelled with [(3)H]ethynylbicycloorthobenzoate (EBOB), a convulsant radioligand. Saturation analysis revealed a homogenous, nanomolar population of [(3)H]...


    pub_type: 杂志文章


    authors: Maksay G,Bíró T

    更新日期:2005-09-01 00:00:00

  • Discriminative stimulus properties of the dopamine D3 receptor agonists, PD128,907 and 7-OH-DPAT: a comparative characterization with novel ligands at D3 versus D2 receptors.

    abstract::Rats were trained to recognize a discriminative stimulus (DS) elicited by the preferential dopamine D3 receptor agonists, PD128,907 (0.16 mg/kg, i.p.) and 7-OH-DPAT (0.16 mg/kg, i.p.). PD128,907 and 7-OH-DPAT showed "full" (> or = 80%) and mutual generalization. Chemically-diverse, preferential D3 versus D2 agonists, ...


    pub_type: 杂志文章


    authors: Millan MJ,Girardon S,Monneyron S,Dekeyne A

    更新日期:2000-02-14 00:00:00

  • mGlu5 function in the nucleus accumbens core during the incubation of methamphetamine craving.

    abstract::Many studies have demonstrated that negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGlu5) reduce cocaine and methamphetamine seeking in extinction-reinstatement animal models of addiction. Less is known about effects of mGlu5 NAMs in abstinence models, particularly for methamphetamine. We u...


    pub_type: 杂志文章


    authors: Murray CH,Christian DT,Milovanovic M,Loweth JA,Hwang EK,Caccamise AJ,Funke JR,Wolf ME

    更新日期:2021-01-12 00:00:00

  • Modulation of the GABAA-like autoreceptor by barbiturates but not by steroids.

    abstract::In slices of cerebral cortex from rat preloaded with [3H]GABA, muscimol produced a concentration-related inhibition of K(+)-evoked release of tritium with a pIC25 value of 7.80 +/- 0.39. Dimethylbarbituric acid (10 and 100 microM) and pentobarbitone (100 microM) significantly increased this value to 8.31 +/- 0.09, 9.9...


    pub_type: 杂志文章


    authors: Ennis C,Minchin MC

    更新日期:1993-04-01 00:00:00

  • Glycinergic synaptic currents in the deep cerebellar nuclei.

    abstract::Despite evidence of local glycinergic circuits in the mature cerebellar nuclei the result of their activation remains unknown. Here, using whole cell recordings in rat cerebellar slices we demonstrated that after postnatal day 17 (>P17) glycinergic IPSCs can be readily evoked in large deep cerebellar nuclear neurons (...


    pub_type: 杂志文章


    authors: Pedroarena CM,Kamphausen S

    更新日期:2008-04-01 00:00:00

  • In vivo chronic nicotine exposure differentially and reversibly affects upregulation and stoichiometry of α4β2 nicotinic receptors in cortex and thalamus.

    abstract::Studies with heterologous expression systems have shown that the α4β2 nicotinic acetylcholine receptor (nAChR) subtype can exist in two stoichiometries (with two [(α4)2(β2)3] or three [(α4)3(β2)2] copies of the α subunit in the receptor pentamer) which have different pharmacological and functional properties and are d...


    pub_type: 杂志文章


    authors: Fasoli F,Moretti M,Zoli M,Pistillo F,Crespi A,Clementi F,Mc Clure-Begley T,Marks MJ,Gotti C

    更新日期:2016-09-01 00:00:00

  • Comparison of the actions of phencyclidine and sigma ligands on CA1 hippocampal pyramidal neurons in the rat.

    abstract::To compare the actions of prototypic drugs which are selective for phencyclidine and sigma receptors, the electrophysiological effects of phencyclidine (PCP),3-[3-hydroxyphenyl]-N-(1-propyl)piperidine [+)3-PPP), and 1,3-di(2-tolyl)guanidine (DTG) on CA1 hippocampal pyramidal neurons were examined. A wide range of conc...


    pub_type: 杂志文章


    authors: Malouf AT,Swearengen E,Chavkin C

    更新日期:1988-11-01 00:00:00

  • Effects of histamine H3 receptors on chemical hyperalgesia in diabetic rats.

    abstract::There is considerable interest in histamine H3 receptors as emerging pharmaceutical targets recently. Diabetic rats display increased pain responses following the injection of formalin into the paw suggesting the presence of hyperalgesia. In this study, the efficacy of systemic administration of selective H3 receptor ...


    pub_type: 杂志文章


    authors: Hasanein P

    更新日期:2011-05-01 00:00:00

  • Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor.

    abstract::Because of the claim that ibogaine suppresses the symptoms of "narcotic withdrawal" in humans, the effect of ibogaine on naltrexone-precipitated withdrawal signs in morphine-dependent rats was assessed. Morphine was administered subcutaneously through implanted silicone reservoirs for 5 days. Ibogaine (20, 40 or 80 mg...


    pub_type: 杂志文章


    authors: Glick SD,Rossman K,Rao NC,Maisonneuve IM,Carlson JN

    更新日期:1992-05-01 00:00:00

  • The acute effects of zolpidem compared to diazepam and lorazepam using radiotelemetry.

    abstract::The present study used a radiotelemetric method to compare the muscle relaxant, hypothermic and locomotor depressant actions of the imidazopyridine zolpidem, with those of the benzodiazepines lorazepam and diazepam. Rats, n=7 per group, were divided into 3 dose-dependent treatment groups (highest, middle, and lowest)....


    pub_type: 杂志文章


    authors: Elliot EE,White JM

    更新日期:2001-04-01 00:00:00

  • A legacy of discovery: from monoamines to GABA.

    abstract::Seldom does a single individual have such a profound effect on the development of a scientific discipline as Erminio Costa had on neuropharmacology. During nearly sixty years of research, Costa and his collaborators helped established many of the basic principles of the pharmacodynamic actions of psychotherapeutics. H...


    pub_type: 杂志文章,评审


    authors: Enna SJ

    更新日期:2011-06-01 00:00:00

  • Synaptic transmission at single visualized hippocampal boutons.

    abstract::We have used a focal stimulation method to study neurotransmission at synapses onto hippocampal pyramidal neurons in cultures derived from neonatal rats. Single functional boutons were visualized by activity-dependent preloading with the fluorescent dye FM1-43, then focally stimulated by localized application of eleva...


    pub_type: 杂志文章


    authors: Liu G,Tsien RW

    更新日期:1995-11-01 00:00:00

  • Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens.

    abstract::Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the...


    pub_type: 杂志文章,评审


    authors: Halberstadt AL,Geyer MA

    更新日期:2011-09-01 00:00:00

  • Posterior hypothalamic receptors involved in the cardiovascular changes elicited by electrical stimulation of the rostral ventrolateral medulla.

    abstract::The posterior hypothalamic receptors involved in the cardiovascular responses to electrical stimulation of the rostral ventrolateral medulla were investigated in urethane-anaesthetized rats. Electrical stimulation of the rostral ventrolateral medulla produced a significant increase in systolic blood pressure. This res...


    pub_type: 杂志文章


    authors: Bachelard H,Rivest R,Marsden CA

    更新日期:1991-07-01 00:00:00

  • Synergistic effect of 5-HT1A and σ1 receptor activation on prefrontal dopaminergic transmission under circulating steroid deficiency.

    abstract::Serotonin (5-HT)1A and σ1 receptors have been implicated in psychiatric disorders. We previously found that combined 5-HT reuptake inhibition and σ1 receptor activation has a synergistic effect on prefrontal dopaminergic transmission in adrenalectomized/castrated mice lacking circulating steroid hormones. In the prese...


    pub_type: 杂志文章


    authors: Hiramatsu N,Ago Y,Hasebe S,Nishimura A,Mori K,Takuma K,Matsuda T

    更新日期:2013-12-01 00:00:00

  • Cav1.2 L-type calcium channels regulate stress coping behavior via serotonin neurons.

    abstract::Human genetic variation in the gene CACNA1C, which codes for the alpha-1c subunit of Cav1.2 L-type calcium channels (LTCCs), has been broadly associated with enhanced risk for neuropsychiatric disorders including major depression, bipolar and schizophrenia. Little is known about the specific neural circuits through wh...


    pub_type: 杂志文章


    authors: Ehlinger DG,Commons KG

    更新日期:2019-01-01 00:00:00

  • Serotonergic pharmacology in animal models: from behavioral disorders to dyskinesia.

    abstract::Serotonin (5-HT) dysfunction has been involved in both movement and behavioral disorders. Serotonin pharmacology improves dyskinetic movements as well as depressive, anxious, aggressive and anorexic symptoms. Animal models have been useful to investigate more precisely to what extent 5-HT is involved and whether drugs...


    pub_type: 杂志文章,评审


    authors: Beaudoin-Gobert M,Sgambato-Faure V

    更新日期:2014-06-01 00:00:00

  • How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems.

    abstract::Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving sero...


    pub_type: 历史文章,杂志文章,评审


    authors: Murphy DL,Fox MA,Timpano KR,Moya PR,Ren-Patterson R,Andrews AM,Holmes A,Lesch KP,Wendland JR

    更新日期:2008-11-01 00:00:00

  • Effect of organochlorine insecticides on nicotinic acetylcholine receptor-rich membranes.

    abstract::The so-called generalized polarization (GP) of the fluorescent probe Laurdan and the steady-state fluorescence anisotropy of the probe diphenylhexatriene (DPH) and its phenylpropionic derivative (PA-DPH) were used to study the effects of several organochlorine insecticides of the chlorophenylethane, chlorinated cycloh...


    pub_type: 杂志文章


    authors: Massol RH,Antollini SS,Barrantes FJ

    更新日期:2000-04-03 00:00:00

  • Effect of non-dopaminergic drug treatment on Levodopa induced dyskinesias in MPTP monkeys: common implication of striatal neuropeptides.

    abstract::Dopamine denervation in Parkinson's disease and repeated Levodopa (L-DOPA) administration that induces dyskinesias are associated with an enhancement of basal ganglia neuropeptide transmission. Various adjunct non-dopaminergic treatments to Levodopa were shown to reduce and/or prevent dyskinesias. The aim of this stud...


    pub_type: 杂志文章


    authors: Tamim MK,Samadi P,Morissette M,Grégoire L,Ouattara B,Lévesque D,Rouillard C,Di Paolo T

    更新日期:2010-01-01 00:00:00

  • Early reactions of brain-derived neurotrophic factor in plasma (pBDNF) and outcome to acute antidepressant treatment in patients with Major Depression.

    abstract::In Major Depressive Disorder, a growing data base suggests that the onset of antidepressants' action can be detected by improvement of depressive symptoms in the first 10-14 days of treatment. Previous studies showed that the mean concentration of the brain-derived neurotrophic factor (BDNF) in blood increases during ...


    pub_type: 杂志文章


    authors: Dreimüller N,Schlicht KF,Wagner S,Peetz D,Borysenko L,Hiemke C,Lieb K,Tadić A

    更新日期:2012-01-01 00:00:00