title: The glycine reuptake inhibitor org 25935 interacts with basal and ethanol-induced dopamine release in rat nucleus accumbens.
abstract: BACKGROUND
  The mesolimbic dopamine (DA) projection from the ventral tegmental area to nucleus accumbens (nAc), a central part of the reward system, is activated by ethanol (EtOH) and other drugs of abuse. We have previously demonstrated that the glycine receptor in the nAc and its amino acid agonists may be implicated in the DA activation and reinforcing properties of EtOH. We have also reported that the glycine transporter 1 inhibitor, Org 25935, produces a robust and dose-dependent decrease in EtOH consumption in Wistar rats. The present study explores the interaction between EtOH and Org 25935 with respect to DA levels in the rat nAc.
  
  
  METHODS
  The effects of Org 25935 (6 mg/kg, i.p.) and/or EtOH (2.5 g/kg, i.p.) on accumbal DA levels were examined by means of in vivo microdialysis (coupled to HPLC-ED) in freely moving male Wistar rats. The effect of Org 25935 on accumbal glycine output was also investigated.
  
  
  RESULTS
  Systemic Org 25935 increased DA output in a subpopulation of rats (52% in Experiment 1 and 38% in Experiment 2). In Experiment 2, EtOH produced a significant increase in DA levels in vehicles (35%) and in Org 25935 nonresponders (19%), whereas EtOH did not further increase the DA level in rats responding to Org 25935 (2%). The same dose of Org 25935 increased glycine levels by 87% in nAc.
  
  
  CONCLUSIONS
  This study demonstrates that Org 25935, probably via increased glycine levels, (i) counteracts EtOH-induced increases of accumbal DA levels and (ii) increases basal DA levels in a subpopulation of rats. The results are in line with previous findings and it is suggested that the effects observed involve interference with accumbal GlyRs and are related to the alcohol consumption modulating effect of Org 25935.
authors.affiliation: Section of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg and Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden. helga.lido@neuro.gu.se
authors.forename: Helga Höifödt
authors.initials: HH
authors.lastname: Lidö
authors.forename: Rosita
authors.initials: R
authors.lastname: Stomberg
authors.forename: Anne
authors.initials: A
authors.lastname: Fagerberg
authors.forename: Mia
authors.initials: M
authors.lastname: Ericson
authors.forename: Bo
authors.initials: B
authors.lastname: Söderpalm
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D005998:Glycine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C520612:N-methyl-N-(6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen-2-ylmethyl)aminomethylcarboxylic acid; D018009:Receptors, Glycine; D013764:Tetrahydronaphthalenes; D000431:Ethanol; D005998:Glycine; D004298:Dopamine