267
Views
7
CrossRef citations to date
0
Altmetric
Review

Investigational therapies for the pharmacological treatment of alcoholism

, &

Bibliography

  • Whiteford HA, Degenhardt L, Rehm J, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 2013;382(9904):1575–86
  • McCrady BS, Owens MD, Borders AZ, et al. Psychosocial approaches to alcohol use disorders since 1940: a review. J Stud Alcohol Drugs Suppl 2014;75(Suppl 17):68–78
  • Franck J, Jayaram-Lindstrom N. Pharmacotherapy for alcohol dependence: status of current treatments. Curr Opin Neurobiol 2013;23(4):692–9
  • Rehm J, Shield KD, Rehm MX, et al. Alcohol consumption, alcohol dependence, and attributable burden of disease in Europe: potential gains from effective interventions for alcohol dependence. Centre for Addiction and Mental Health, Toronto, Canada; 2012
  • Leggio L, Kenna GA, Fenton M, et al. Typologies of alcohol dependence. From Jellinek to genetics and beyond. Neuropsychol Rev 2009;19(1):115–29
  • Spanagel R, Noori HR, Heilig M. Stress and alcohol interactions: animal studies and clinical significance. Trends Neurosci 2014;37(4):219–27
  • Przybycien-Szymanska MM, Mott NN, Pak TR. Alcohol dysregulates corticotropin-releasing-hormone (CRH) promoter activity by interfering with the negative glucocorticoid response element (nGRE). PLoS One 2011;6(10):e26647
  • Roberto M, Cruz MT, Gilpin NW, et al. Corticotropin releasing factor-induced amygdala gamma-aminobutyric Acid release plays a key role in alcohol dependence. Biol Psychiatry 2010;67(9):831–9
  • Koob GF. Alcoholism: allostasis and beyond. Alcohol Clin Exp Res 2003;27(2):232–43
  • Koob GF. Brain stress systems in the amygdala and addiction. Brain Res 2009;1293:61–75
  • Roberts AJ, Heyser CJ, Cole M, et al. Excessive ethanol drinking following a history of dependence: animal model of allostasis. Neuropsychopharmacology 2000;22(6):581–94
  • Cippitelli A, Damadzic R, Singley E, et al. Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats. Pharmacol Biochem Behav 2012;100(3):522–9
  • Finn DA, Snelling C, Fretwell AM, et al. Increased drinking during withdrawal from intermittent ethanol exposure is blocked by the CRF receptor antagonist D-Phe-CRF(12-41). Alcohol Clin Exp Res 2007;31(6):939–49
  • Ji D, Gilpin NW, Richardson HN, et al. Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats. Behav Pharmacol 2008;19(1):1–12
  • Lam MP, Gianoulakis C. Effects of corticotropin-releasing hormone receptor antagonists on the ethanol-induced increase of dynorphin A1-8 release in the rat central amygdala. Alcohol 2011;45(7):621–30
  • Rao PS, Sari Y. Glutamate transporter 1: target for the treatment of alcohol dependence. Curr Med Chem 2012;19(30):5148–56
  • Chen X, Michaelis ML, Michaelis EK. Effects of chronic ethanol treatment on the expression of calcium transport carriers and NMDA/glutamate receptor proteins in brain synaptic membranes. J Neurochem 1997;69(4):1559–69
  • Siggins GR, Martin G, Roberto M, et al. Glutamatergic transmission in opiate and alcohol dependence. Ann N Y Acad Sci 2003;1003:196–211
  • Quintero GC. Role of nucleus accumbens glutamatergic plasticity in drug addiction. Neuropsychiatr Dis Treat 2013;9:1499–512
  • Kalivas PW, Volkow ND. New medications for drug addiction hiding in glutamatergic neuroplasticity. Mol Psychiatry 2011;16(10):974–86
  • Sari Y. Potential therapeutic role of glutamate transporter 1 for the treatment of alcohol dependence. OA Alcohol 2013;1(1):6
  • Li J, Nie H, Bian W, et al. Microinjection of glycine into the ventral tegmental area selectively decreases ethanol consumption. J Pharmacol Exp Ther 2012;341(1):196–204
  • Szumlinski KK, Lominac KD, Oleson EB, et al. Homer2 is necessary for EtOH-induced neuroplasticity. J Neurosci 2005;25(30):7054–61
  • Seal RP, Amara SG. Excitatory amino acid transporters: a family in flux. Annu Rev Pharmacol Toxicol 1999;39:431–56
  • Nakagawa T, Fujio M, Ozawa T, et al. Effect of MS-153, a glutamate transporter activator, on the conditioned rewarding effects of morphine, methamphetamine and cocaine in mice. Behav Brain Res 2005;156(2):233–9
  • Sari Y, Smith KD, Ali PK, et al. Upregulation of GLT1 attenuates cue-induced reinstatement of cocaine-seeking behavior in rats. J Neurosci 2009;29(29):9239–43
  • Lewerenz J, Albrecht P, Tien ML, et al. Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro. J Neurochem 2009;111(2):332–43
  • Rodd ZA, Bell RL, McQueen VK, et al. Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol. Alcohol Clin Exp Res 2005;29(3):358–66
  • Rodd ZA, Bell RL, McQueen VK, et al. Prolonged increase in the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol following repeated exposure to cycles of ethanol access and deprivation. J Pharmacol Exp Ther 2005;315(2):648–57
  • Sari Y, Sakai M, Weedman JM, et al. Ceftriaxone, a beta-lactam antibiotic, reduces ethanol consumption in alcohol-preferring rats. Alcohol Alcohol 2011;46(3):239–46
  • Rao PS, Sari Y. Effects of ceftriaxone on chronic ethanol consumption: a potential role for xCT and GLT1 modulation of glutamate levels in male P rats. J Mol Neurosci 2014;54(1):71–7
  • Qrunfleh AM, Alazizi A, Sari Y. Ceftriaxone, a beta-lactam antibiotic, attenuates relapse-like ethanol-drinking behavior in alcohol-preferring rats. J Psychopharmacol 2013;27(6):541–9
  • Conn PJ, Pin JP. Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 1997;37:205–37
  • Sannibale C, Hall W. An evaluation of Cloninger’s typology of alcohol abuse. Addiction 1998;93(8):1241–9
  • Kupila J, Karkkainen O, Laukkanen V, et al. mGluR1/5 receptor densities in the brains of alcoholic subjects: a whole-hemisphere autoradiography study. Psychiatry Res 2013;212(3):245–50
  • Carroll FI. Antagonists at metabotropic glutamate receptor subtype 5: structure activity relationships and therapeutic potential for addiction. Ann N Y Acad Sci 2008;1141:221–32
  • Cozzoli DK, Courson J, Caruana AL, et al. Nucleus accumbens mGluR5-associated signaling regulates binge alcohol drinking under drinking-in-the-dark procedures. Alcohol Clin Exp Res 2012;36(9):1623–33
  • Hodge CW, Miles MF, Sharko AC, et al. The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice. Psychopharmacology (Berl) 2006;183(4):429–38
  • Lominac KD, Kapasova Z, Hannun RA, et al. Behavioral and neurochemical interactions between Group 1 mGluR antagonists and ethanol: potential insight into their anti-addictive properties. Drug Alcohol Depend 2006;85(2):142–56
  • Schroeder JP, Overstreet DH, Hodge CW. The mGluR5 antagonist MPEP decreases operant ethanol self-administration during maintenance and after repeated alcohol deprivations in alcohol-preferring (P) rats. Psychopharmacology (Berl) 2005;179(1):262–70
  • Backstrom P, Hyytia P. Ionotropic glutamate receptor antagonists modulate cue-induced reinstatement of ethanol-seeking behavior. Alcohol Clin Exp Res 2004;28(4):558–65
  • Sinclair CM, Cleva RM, Hood LE, et al. mGluR5 receptors in the basolateral amygdala and nucleus accumbens regulate cue-induced reinstatement of ethanol-seeking behavior. Pharmacol Biochem Behav 2012;101(3):329–35
  • Ferraro L, Loche A, Beggiato S, et al. The new compound GET73, N-[(4-trifluoromethyl)benzyl]4-methoxybutyramide, Regulates hippocampal Aminoacidergic transmission possibly via an allosteric modulation of mGlu5 receptor. Behavioural evidence of its "anti-alcohol" and anxiolytic properties. Curr Med Chem 2013;20(27):3339–57
  • Minami K, Gereau RWIV, Minami M, et al. Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes. Mol Pharmacol 1998;53(1):148–56
  • Cozzoli DK, Goulding SP, Zhang PW, et al. Binge drinking upregulates accumbens mGluR5-Homer2-PI3K signaling: functional implications for alcoholism. J Neurosci 2009;29(27):8655–68
  • Niswender CM, Conn PJ. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 2010;50:295–322
  • Besheer J, Faccidomo S, Grondin JJ, et al. Regulation of motivation to self-administer ethanol by mGluR5 in alcohol-preferring (P) rats. Alcohol Clin Exp Res 2008;32(2):209–21
  • Besheer J, Faccidomo S, Grondin JJ, et al. Effects of mGlu1-receptor blockade on ethanol self-administration in inbred alcohol-preferring rats. Alcohol 2008;42(1):13–20
  • Lum EN, Campbell RR, Rostock C, et al. mGluR1 within the nucleus accumbens regulates alcohol intake in mice under limited-access conditions. Neuropharmacology 2014;79:679–87
  • Weitlauf C, Woodward JJ. Ethanol selectively attenuates NMDAR-mediated synaptic transmission in the prefrontal cortex. Alcohol Clin Exp Res 2008;32(4):690–8
  • Jansen M, Dannhardt G. Antagonists and agonists at the glycine site of the NMDA receptor for therapeutic interventions. Eur J Med Chem 2003;38(7-8):661–70
  • Lockridge A, Romero G, Harrington J, et al. Timing-dependent reduction in ethanol sedation and drinking preference by NMDA receptor co-agonist d-serine. Alcohol 2012;46(4):389–400
  • Debrouse L, Hurd B, Kiselycznyk C, et al. Probing the modulation of acute ethanol intoxication by pharmacological manipulation of the NMDAR glycine co-agonist site. Alcohol Clin Exp Res 2013;37(2):223–33
  • Woodward JJ, Brown L, Gonzales RA. Modulation of ethanol-induced inhibition of N-methyl-D-aspartate-stimulated neurotransmitter release by glycine. Alcohol Alcohol Suppl 1991;1:177–80
  • Rabe CS, Tabakoff B. Glycine site-directed agonists reverse the actions of ethanol at the N-methyl-D-aspartate receptor. Mol Pharmacol 1990;38(6):753–7
  • Kiefer F, Jahn H, Koester A, et al. Involvement of NMDA receptors in alcohol-mediated behavior: mice with reduced affinity of the NMDA R1 glycine binding site display an attenuated sensitivity to ethanol. Biol Psychiatry 2003;53(4):345–51
  • Schuckit MA. Biological, psychological and environmental predictors of the alcoholism risk: a longitudinal study. J Stud Alcohol 1998;59(5):485–94
  • Li Z, Zharikova A, Vaughan CH, et al. Intermittent high-dose ethanol exposures increase motivation for operant ethanol self-administration: possible neurochemical mechanism. Brain Res 2010;1310:142–53
  • Ericson M, Chau P, Adermark L, et al. Rising taurine and ethanol concentrations in nucleus accumbens interact to produce the dopamine-activating effects of alcohol. Adv Exp Med Biol 2013;775:215–23
  • Blednov YA, Benavidez JM, Homanics GE, et al. Behavioral characterization of knockin mice with mutations M287L and Q266I in the glycine receptor alpha1 subunit. J Pharmacol Exp Ther 2012;340(2):317–29
  • Morud J, Adermark L, Ericson M, et al. Alterations in ethanol-induced accumbal transmission after acute and long-term zinc depletion. Addict Biol 2013. [Epub ahead of print]
  • McCracken LM, Blednov YA, Trudell JR, et al. Mutation of a zinc-binding residue in the glycine receptor alpha1 subunit changes ethanol sensitivity in vitro and alcohol consumption in vivo. J Pharmacol Exp Ther 2013;344(2):489–500
  • Chau P, Hoifodt-Lido H, Lof E, et al. Glycine receptors in the nucleus accumbens involved in the ethanol intake-reducing effect of acamprosate. Alcohol Clin Exp Res 2010;34(1):39–45
  • Aguayo LG, Castro P, Mariqueo T, et al. Altered sedative effects of ethanol in mice with alpha1 glycine receptor subunits that are insensitive to Gbetagamma modulation. Neuropsychopharmacology 2014. [Epub ahead of print]
  • Molander A, Lido HH, Lof E, et al. The glycine reuptake inhibitor Org 25935 decreases ethanol intake and preference in male wistar rats. Alcohol Alcohol 2007;42(1):11–18
  • Lido HH, Marston H, Ericson M, et al. The glycine reuptake inhibitor Org24598 and acamprosate reduce ethanol intake in the rat; tolerance development to acamprosate but not to Org24598. Addict Biol 2012;17(5):897–907
  • Vengeliene V, Leonardi-Essmann F, Sommer WH, et al. Glycine transporter-1 blockade leads to persistently reduced relapse-like alcohol drinking in rats. Biol Psychiatry 2010;68(8):704–11
  • Lido HH, Stomberg R, Fagerberg A, et al. The glycine reuptake inhibitor org 25935 interacts with basal and ethanol-induced dopamine release in rat nucleus accumbens. Alcohol Clin Exp Res 2009;33(7):1151–7
  • Narendran R, Mason NS, Paris J, et al. Decreased prefrontal cortical dopamine transmission in alcoholism. Am J Psychiatry 2014;171(8):881–8
  • Wiesbeck GA, Weijers HG, Lesch OM, et al. Flupenthixol decanoate and relapse prevention in alcoholics: results from a placebo-controlled study. Alcohol Alcohol 2001;36(4):329–34
  • Bender S, Scherbaum N, Soyka M, et al. The efficacy of the dopamine D2/D3 antagonist tiapride in maintaining abstinence: a randomized, double-blind, placebo-controlled trial in 299 alcohol-dependent patients. Int J Neuropsychopharmacol 2007;10(5):653–60
  • Heidbreder CA, Andreoli M, Marcon C, et al. Evidence for the role of dopamine D3 receptors in oral operant alcohol self-administration and reinstatement of alcohol-seeking behavior in mice. Addict Biol 2007;12(1):35–50
  • Leggio GM, Camillieri G, Platania CB, et al. Dopamine D3 receptor is necessary for ethanol consumption: an approach with buspirone. Neuropsychopharmacology 2014;39(8):2017–28
  • Martinotti G, Di Nicola M, Janiri L. Efficacy and safety of aripiprazole in alcohol dependence. Am J Drug Alcohol Abuse 2007;33(3):393–401
  • Martinotti G, Di Nicola M, Di Giannantonio M, et al. Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. naltrexone. J Psychopharmacol 2009;23(2):123–9
  • Steensland P, Fredriksson I, Holst S, et al. The monoamine stabilizer (-)-OSU6162 attenuates voluntary ethanol intake and ethanol-induced dopamine output in nucleus accumbens. Biol Psychiatry 2012;72(10):823–31
  • Heilig M, Schank JR. Kappa-opioid receptor antagonism: a mechanism for treatment of relief drinking? Biol Psychiatry 2014;75(10):750–1
  • Walker BM, Koob GF. Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence. Neuropsychopharmacology 2008;33(3):643–52
  • Walker BM, Zorrilla EP, Koob GF. Systemic kappa-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats. Addict Biol 2011;16(1):116–19
  • Cashman JR, Azar M. Potent inhibition of alcohol self-administration in alcohol-preferring rats by a kappa opioid receptor antagonist. J Pharmacol Exp Ther 2014;350(1):171–80
  • Rorick-Kehn LM, Witkin JM, Statnick MA, et al. LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders. Neuropharmacology 2014;77:131–44
  • Mitchell JM, Liang MT, Fields HL. A single injection of the kappa opioid antagonist norbinaltorphimine increases ethanol consumption in rats. Psychopharmacology (Berl) 2005;182(3):384–92
  • Schank JR, Goldstein AL, Rowe KE, et al. The kappa opioid receptor antagonist JDTic attenuates alcohol seeking and withdrawal anxiety. Addict Biol 2012;17(3):634–47
  • Kissler JL, Sirohi S, Reis DJ, et al. The one-two punch of alcoholism: role of central amygdala dynorphins/kappa-opioid receptors. Biol Psychiatry 2014;75(10):774–82
  • Nealey KA, Smith AW, Davis SM, et al. kappa-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats. Neuropharmacology 2011;61(1-2):35–42
  • Morani AS, Ewald A, Prevatt-Smith KM, et al. The 2-methoxy methyl analogue of salvinorin A attenuates cocaine-induced drug seeking and sucrose reinforcements in rats. Eur J Pharmacol 2013;720(1-3):69–76
  • Wong CJ, Witcher J, Mallinckrodt C, et al. A phase 2, placebo-controlled study of the opioid receptor antagonist LY2196044 for the treatment of alcohol dependence. Alcohol Clin Exp Res 2014;38(2):511–20
  • Colombo G, Orru A, Lai P, et al. The cannabinoid CB1 receptor antagonist, rimonabant, as a promising pharmacotherapy for alcohol dependence: preclinical evidence. Mol Neurobiol 2007;36(1):102–12
  • Soyka M, Koller G, Schmidt P, et al. Cannabinoid receptor 1 blocker rimonabant (SR 141716) for treatment of alcohol dependence: results from a placebo-controlled, double-blind trial. J Clin Psychopharmacol 2008;28(3):317–24
  • George DT, Herion DW, Jones CL, et al. Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers. Psychopharmacology (Berl) 2010;208(1):37–44
  • Vasiljevik T, Franks LN, Ford BM, et al. Design, synthesis, and biological evaluation of aminoalkylindole derivatives as cannabinoid receptor ligands with potential for treatment of alcohol abuse. J Med Chem 2013;56(11):4537–50
  • Mendez-Diaz M, Caynas Rojas S, Gomez Armas D, et al. Endocannabinoid/GABA interactions in the entopeduncular nucleus modulates alcohol intake in rats. Brain Res Bull 2013;91(31):7
  • Panlilio LV, Justinova Z, Goldberg SR. Inhibition of FAAH and activation of PPAR: new approaches to the treatment of cognitive dysfunction and drug addiction. Pharmacol Ther 2013;138(1):84–102
  • Cippitelli A, Cannella N, Braconi S, et al. Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat. Psychopharmacology (Berl) 2008;198(4):449–60
  • Hillemacher T, Frieling H, Hartl T, et al. Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving. J Psychiatr Res 2009;43(4):388–92
  • Heberlein A, Muschler M, Frieling H, et al. Epigenetic down regulation of nerve growth factor during alcohol withdrawal. Addict Biol 2013;18(3):508–10
  • Sakharkar AJ, Zhang H, Tang L, et al. Histone deacetylases (HDAC)-induced histone modifications in the amygdala: a role in rapid tolerance to the anxiolytic effects of ethanol. Alcohol Clin Exp Res 2012;36(1):61–71
  • Pascual M, Do Couto BR, Alfonso-Loeches S, et al. Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning. Neuropharmacology 2012;62(7):2309–19
  • Botia B, Legastelois R, Alaux-Cantin S, et al. Expression of ethanol-induced behavioral sensitization is associated with alteration of chromatin remodeling in mice. PLoS One 2012;7(10):e47527
  • Legastelois R, Botia B, Naassila M. Blockade of ethanol-induced behavioral sensitization by sodium butyrate: descriptive analysis of gene regulations in the striatum. Alcohol Clin Exp Res 2013;37(7):1143–53
  • Warnault V, Darcq E, Levine A, et al. Chromatin remodeling–a novel strategy to control excessive alcohol drinking. Transl Psychiatry 2013;3:e231
  • Engel JA, Jerlhag E. Role of appetite-regulating peptides in the pathophysiology of addiction: implications for pharmacotherapy. CNS Drugs 2014. [Epub ahead of print]
  • Leggio L. Role of the ghrelin system in alcoholism: acting on the growth hormone secretagogue receptor to treat alcohol-related diseases. Drug News Perspect 2010;23(3):157–66
  • Leggio L, Zywiak WH, Fricchione SR, et al. Intravenous ghrelin administration increases alcohol craving in alcohol-dependent heavy drinkers: a preliminary investigation. Biol Psychiatry 2014. [Epub ahead of print]
  • Le AD, Funk D, Juzytsch W, et al. Effect of prazosin and guanfacine on stress-induced reinstatement of alcohol and food seeking in rats. Psychopharmacology (Berl) 2011;218(1):89–99
  • Verplaetse TL, Rasmussen DD, Froehlich JC, et al. Effects of prazosin, an alpha1-adrenergic receptor antagonist, on the seeking and intake of alcohol and sucrose in alcohol-preferring (P) rats. Alcohol Clin Exp Res 2012;36(5):881–6
  • Froehlich JC, Hausauer BJ, Federoff DL, et al. Prazosin reduces alcohol drinking throughout prolonged treatment and blocks the initiation of drinking in rats selectively bred for high alcohol intake. Alcohol Clin Exp Res 2013;37(9):1552–60
  • Froehlich JC, Hausauer BJ, Rasmussen DD. Combining naltrexone and prazosin in a single oral medication decreases alcohol drinking more effectively than does either drug alone. Alcohol Clin Exp Res 2013;37(10):1763–70
  • Simpson TL, Saxon AJ, Meredith CW, et al. A pilot trial of the alpha-1 adrenergic antagonist, prazosin, for alcohol dependence. Alcohol Clin Exp Res 2009;33(2):255–63
  • Fox HC, Anderson GM, Tuit K, et al. Prazosin effects on stress- and cue-induced craving and stress response in alcohol-dependent individuals: preliminary findings. Alcohol Clin Exp Res 2012;36(2):351–60
  • O’Neil ML, Beckwith LE, Kincaid CL, et al. The alpha1-adrenergic receptor antagonist, doxazosin, reduces alcohol drinking in alcohol-preferring (P) Rats. Alcohol Clin Exp Res 2013;37(2):202–12
  • Leggio L, Kenna GA. Commentary: doxasozin for alcoholism. Alcohol Clin Exp Res 2013;37(2):191–3
  • Shorter D, Lindsay JA, Kosten TR. The alpha-1 adrenergic antagonist doxazosin for treatment of cocaine dependence: a pilot study. Drug Alcohol Depend 2013;131(1-2):66–70
  • Correa M, Salamone JD, Segovia KN, et al. Piecing together the puzzle of acetaldehyde as a neuroactive agent. Neurosci Biobehav Rev 2012;36(1):404–30
  • Peana AT, Assaretti AR, Muggironi G, et al. Reduction of ethanol-derived acetaldehyde induced motivational properties by L-cysteine. Alcohol Clin Exp Res 2009;33(1):43–8
  • Peana AT, Enrico P, Assaretti AR, et al. Key role of ethanol-derived acetaldehyde in the motivational properties induced by intragastric ethanol: a conditioned place preference study in the rat. Alcohol Clin Exp Res 2008;32(2):249–58
  • Peana AT, Giugliano V, Rosas M, et al. Effects of L-cysteine on reinstatement of ethanol-seeking behavior and on reinstatement-elicited extracellular signal-regulated kinase phosphorylation in the rat nucleus accumbens shell. Alcohol Clin Exp Res 2013;37(Suppl 1):E329–37
  • Enrico P, Sirca D, Mereu M, et al. Acetaldehyde sequestering prevents ethanol-induced stimulation of mesolimbic dopamine transmission. Drug Alcohol Depend 2009;100(3):265–71
  • Sarruf DA, Yu F, Nguyen HT, et al. Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasis. Endocrinology 2009;150(2):707–12
  • Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem 2008;77:289–312
  • Maeda T, Kiguchi N, Fukazawa Y, et al. Peroxisome proliferator-activated receptor gamma activation relieves expression of behavioral sensitization to methamphetamine in mice. Neuropsychopharmacology 2007;32(5):1133–40
  • Stopponi S, de Guglielmo G, Somaini L, et al. Activation of PPARgamma by pioglitazone potentiates the effects of naltrexone on alcohol drinking and relapse in msP rats. Alcohol Clin Exp Res 2013;37(8):1351–60
  • Stopponi S, Somaini L, Cippitelli A, et al. Activation of nuclear PPARgamma receptors by the antidiabetic agent pioglitazone suppresses alcohol drinking and relapse to alcohol seeking. Biol Psychiatry 2011;69(7):642–9
  • Nikolaev SV, Bychkov ER, Lebedev AA, et al. Mechanisms of the influences of the central administration of substance P on ethanol consumption in chronically alcoholic rats. Neurosci Behav Physiol 2003;33(9):905–9
  • Schank JR, King CE, Sun H, et al. The role of the neurokinin-1 receptor in stress-induced reinstatement of alcohol and cocaine seeking. Neuropsychopharmacology 2014;39(5):1093–101
  • Ebner K, Muigg P, Singewald G, et al. Substance P in stress and anxiety: NK-1 receptor antagonism interacts with key brain areas of the stress circuitry. Ann N Y Acad Sci 2008;1144:61–73
  • George DT, Gilman J, Hersh J, et al. Neurokinin 1 receptor antagonism as a possible therapy for alcoholism. Science 2008;319(5869):1536–9
  • Thorsell A, Schank JR, Singley E, et al. Neurokinin-1 receptors (NK1R:s), alcohol consumption, and alcohol reward in mice. Psychopharmacology (Berl) 2010;209(1):103–11
  • Schank JR, Pickens CL, Rowe KE, et al. Stress-induced reinstatement of alcohol-seeking in rats is selectively suppressed by the neurokinin 1 (NK1) antagonist L822429. Psychopharmacology (Berl) 2011;218(1):111–19
  • Barbier E, Vendruscolo LF, Schlosburg JE, et al. The NK1 receptor antagonist L822429 reduces heroin reinforcement. Neuropsychopharmacology 2013;38(6):976–84
  • Jones JD, Speer T, Comer SD, et al. Opioid-like effects of the neurokinin 1 antagonist aprepitant in patients maintained on and briefly withdrawn from methadone. Am J Drug Alcohol Abuse 2013;39(2):86–91
  • Walsh SL, Heilig M, Nuzzo PA, et al. Effects of the NK1 antagonist, aprepitant, on response to oral and intranasal oxycodone in prescription opioid abusers. Addict Biol 2013;18(2):332–43
  • Addolorato G, Leggio L. Safety and efficacy of baclofen in the treatment of alcohol-dependent patients. Curr Pharm Des 2010;16(19):2113–17
  • Addolorato G, Leggio L, Ferrulli A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet 2007;370(9603):1915–22
  • Hwa LS, Kalinichev M, Haddouk H, et al. Reduction of excessive alcohol drinking by a novel GABAB receptor positive allosteric modulator ADX71441 in mice. Psychopharmacology (Berl) 2014;231(2):333–43
  • Maccioni P, Thomas AW, Carai MA, et al. The positive allosteric modulator of the GABA(B) receptor, rac-BHFF, suppresses alcohol self-administration. Drug Alcohol Depend 2010;109(1-3):96–103
  • Loi B, Maccioni P, Lobina C, et al. Reduction of alcohol intake by the positive allosteric modulator of the GABA(B) receptor, rac-BHFF, in alcohol-preferring rats. Alcohol 2013;47(1):69–73
  • Martinotti G, Di Nicola M, Tedeschi D, et al. Pregabalin versus naltrexone in alcohol dependence: a randomised, double-blind, comparison trial. J Psychopharmacol 2010;24(9):1367–74
  • Salome N, Tasiemski A, Dutriez I, et al. Immune challenge induces differential corticosterone and interleukin-6 responsiveness in rats bred for extremes in anxiety-related behavior. Neuroscience 2008;151(4):1112–18
  • Lee MR, Leggio L. Combined pharmacotherapies for the management of alcoholism: rationale and evidence to date. CNS Drugs 2014;28(2):107–19
  • NICE. Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. NICE; clinical guideline 115 2011
  • Krampe H, Stawicki S, Hoehe MR, et al. Outpatient Long-term Intensive Therapy for Alcoholics (OLITA): a successful biopsychosocial approach to the treatment of alcoholism. Dialogues Clin Neurosci 2007;9(4):399–412
  • Mann K, Bladstrom A, Torup L, et al. Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. Biol Psychiatry 2013;73(8):706–13

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.