The glycine reuptake inhibitor Org 25935 decreases ethanol intake and preference in male wistar rats.
Previous findings from our group indicate that accumbal glycine receptors (GlyRs) are involved in mediating the dopamine (DA) activating effects of ethanol (EtOH), and that administration of glycine locally into the nucleus accumbens (nAc) reduces EtOH consumption in EtOH high-preferring rats.


OBJECTIVE
The present study examines the influence of a systemically administered glycine reuptake inhibitor, Org 25935, on EtOH preference and intake, in male Wistar rats with an EtOH preference >60% (during continuous access to a bottle of EtOH, 6% v/v, and a bottle of water), called EP>60 rats, as well as in animals with an EtOH preference <60%, called EP<60 rats. Org 25935 is an inhibitor of the glycine transporter 1 (GlyT1) protein with negligible action on the glycine transporter 2 (GlyT2) protein.


METHODS
Both EP>60 and EP<60 rats were limited to drink 2.5 h/day. Org 25935 or vehicle was administered intraperitoneally approximately 40 min before the rats were presented to a choice of drinking EtOH or water.


RESULTS
Org 25935 decreased EtOH intake and EtOH preference, as compared with vehicle, whereas water intake was unaffected. This effect was dose-dependent, developed gradually and was sustained for up to 40 days, also after introduction of an alcohol deprivation period.


CONCLUSIONS
It is suggested that Org 25935, and possibly also other GlyT1 inhibitors, can represent a new pharmacological treatment principle for alcohol dependence or abuse.
Molander
Anna
A
Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, Sahlgrenska Academy, Box 410, 405 30 Gothenburg, Sweden.
Lidö
Helga Höifödt
HH
Löf
Elin
E
Ericson
Mia
M
Söderpalm
Bo
B
D000428:Alcohol Drinking / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018684:Glycine Agents / Q000494:pharmacology*; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D018684:Glycine Agents; 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; C493269:Slc6a5 protein, rat; C493266:Slc6a9 protein, rat; D013764:Tetrahydronaphthalenes; D004298:Dopamine