Glycine transporter-1 blockade leads to persistently reduced relapse-like alcohol drinking in rats

Biological Psychiatry
Valentina VengelieneRainer Spanagel

Abstract

Residual dysfunction of multiple neurotransmitter systems due to chronic alcohol use is likely responsible for the occurrence of compulsive alcohol seeking during abstinence and relapse behavior. There is increasing evidence that glycine, which activates both glycine and N-methyl-D-aspartate receptors, contributes to excessive alcohol consumption. We therefore hypothesized that the blockade of glycine transporter 1 might interfere with compulsive alcohol consumption and relapse behavior. We used our animal model of alcoholism--long-term alcohol consumption with repeated deprivation phases in rats--to study the effects of a selective blocker of glycine transporter 1 Org25935. The abstinence-promoting drug acamprosate was used as a reference compound. Subsequently, we examined alterations in dorsal striatal gene expression caused by chronic ethanol (EtOH) consumption, focusing on glycinergic and glutamatergic signaling-related genes. Gene expression profiles of Org25935-treated EtOH-drinking rats were compared with vehicle-treated EtOH-drinking versus age-matched EtOH-naive rats. We found that repeated treatment with Org25935 reduced compulsive relapse-like drinking without the development of tolerance. Importantly, these antirel...Continue Reading

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Citations

Sep 3, 2013·Psychopharmacology·Andrew HolmesJohn H Krystal
Nov 25, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Anna MolanderRainer Spanagel
May 3, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Stéphanie Perreau-LenzRainer Spanagel
Nov 1, 2013·Nature Reviews. Drug Discovery·Robert J Harvey, Benjamin K Yee
Nov 3, 2010·Addiction Biology·Rainer SpanagelAndreas Zimmer
Nov 1, 2011·The Journal of Pharmacology and Experimental Therapeutics·Yuri A BlednovR Adron Harris
Aug 29, 2014·Expert Opinion on Investigational Drugs·Thomas HillemacherAnnemarie Heberlein
Jul 29, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Valentina VengelieneAnton Bespalov
Sep 6, 2015·Journal of Neurochemistry·Valentina VengelieneRainer Spanagel
Mar 24, 2012·Biological Psychiatry·Laura H CorbitPatricia H Janak
Sep 1, 2012·Alcoholism, Clinical and Experimental Research·Lauren DebrouseAndrew Holmes
Nov 29, 2013·Addiction Biology·Rainer SpanagelEske M Derks
Oct 15, 2013·Alcoholism, Clinical and Experimental Research·Valentina VengelieneRainer Spanagel
Dec 19, 2014·The International Journal of Neuropsychopharmacology·Claudia ChauvetMarcello Solinas
Jan 26, 2018·The Journal of Pharmacology and Experimental Therapeutics·Valentina VengelieneRainer Spanagel
Aug 24, 2017·Alcoholism, Clinical and Experimental Research·Bo SöderpalmMia Ericson
Aug 31, 2020·Alcoholism, Clinical and Experimental Research·Eliza R McColl, Micheline Piquette-Miller
Feb 6, 2017·Journal of Neural Transmission·Helga Höifödt LidöBo Söderpalm
May 6, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Marcus W MeinhardtRainer Spanagel
Dec 23, 2020·Journal of Neural Transmission·Yasmin OlssonBo Söderpalm
Dec 2, 2017·Pharmacology & Therapeutics·Mohammed AkbarAntonio Noronha

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