Glycine receptors involved in acamprosate's modulation of accumbal dopamine levels: an in vivo microdialysis study.
BACKGROUND
Glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA) have been suggested to be involved in the positive reinforcing and dopamine elevating effects of ethanol. Recent studies have also shown that ethanol high-preferring rats substantially decrease their ethanol intake when treated with a glycine transporter 1 inhibitor (ORG 25935). Acamprosate, a drug used for relapse prevention in treatment of alcohol dependence, has also been demonstrated to elevate extracellular dopamine levels in the nAc. However, the underlying mechanism of action of acamprosate is not fully understood. Here we investigated whether acamprosate interferes with a neuronal circuitry that previously has been demonstrated to be involved in the dopamine elevating effects of ethanol and taurine.


METHODS
In vivo microdialysis in freely moving rats was used to assess accumbal dopamine levels before and during local (nAc) or systemic administration of acamprosate.


RESULTS
Perfusion of 0.5 mM acamprosate in the nAc significantly increased dopamine levels. Pretreatment either with 10 microM strychnine in the nAc or 100 microM mecamylamine in the VTA, completely antagonized the acamprosate-induced elevation of accumbal dopamine levels. Also, systemic acamprosate administration elevated accumbal dopamine output, an effect that was abolished by local (nAc) pretreatment with 10 microM strychnine.


CONCLUSIONS
These results suggest that both systemic and local application of acamprosate elevate extracellular dopamine levels in the nAc by activating accumbal GlyRs, and, secondarily, tegmental nAChRs.
Addiction Biology Unit, Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden. peipei.chau@neuro.gu.se
Peipei
P
Chau
Rosita
R
Stomberg
Anne
A
Fagerberg
Bo
B
Söderpalm
Mia
M
Ericson
D000077443:Acamprosate; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D045604:Extracellular Fluid / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000502:physiology*; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D018009:Receptors, Glycine; D013654:Taurine; D000077443:Acamprosate; D004298:Dopamine