title: Rasgrf2 controls dopaminergic adaptations to alcohol in mice.
abstract: Alcohol abuse leads to serious health problems with no effective treatment available. Recent evidence suggests a role for ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) in alcoholism. Rasgrf2 is a calcium sensor and MAPK/ERK activating protein, which has been linked to neurotransmitter release and monoaminergic receptor adaptations. Rasgrf2 knock out (KO) mice do not develop a dopamine response in the nucleus accumbens after an alcohol challenge and show a reduced consumption of alcohol. The present study aims to further characterise the role of Rasgrf2 in dopaminergic activation beyond the nucleus accumbens following alcohol treatment. Using in vivo microdialysis we found that alcohol induces alterations in dopamine levels in the dorsal striatum between wildtype (WT) and Rasgrf2 KO mice. There was no difference in the expression of dopamine transporter (DAT), dopamine receptor regulating factor (DRRF), or dopamine D2 receptor (DRD2) mRNA in the brain between Rasgrf2 KO and WT mice. After sub-chronic alcohol treatment, DAT and DRRF, but not DRD2 mRNA expression differed between WT and Rasgrf2 KO mice. Brain adaptations were positively correlated with splenic expression levels. These data suggest that Rasgrf2 controls dopaminergic signalling and adaptations to alcohol also in other brain regions, beyond the nucleus accumbens.
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Alanna C
authors.initials: AC
authors.lastname: Easton
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rotter
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK; School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Lourdusamy
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Sylvane
authors.initials: S
authors.lastname: Desrivières
authors.affiliation: CIC-IBMCC, University of Salamanca - CSIC, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Medarde
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Biermann
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Cathy
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: CIC-IBMCC, University of Salamanca - CSIC, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Santos
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK; Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany. Electronic address: Christian.Mueller@uk-erlangen.de.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Müller
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D020663:ras Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D050483:Dopamine Plasma Membrane Transport Proteins; C486609:Klf16 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; C504491:Rasgrf2 protein, mouse; D017448:Receptors, Dopamine D2; D020663:ras Guanine Nucleotide Exchange Factors; D000431:Ethanol; D004298:Dopamine
keywords: Alcohol; Dopamine; Gene expression; Microdialysis; Rasgrf2; Striatum