Glycine receptors in the nucleus accumbens involved in the ethanol intake-reducing effect of acamprosate.
BACKGROUND
We have previously demonstrated that strychnine-sensitive glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area are involved in mediating ethanol (EtOH)-induced elevation of dopamine in the rat mesolimbic dopamine system. This neuronal circuitry was also demonstrated to mediate dopamine elevation in the nAc after both taurine, an endogenous agonist of GlyRs, and acamprosate, a synthetic derivate of homotaurine. The aim of this study was to investigate whether the EtOH intake-reducing effect of acamprosate involves accumbal GlyRs.


METHODS
For this purpose, we used a voluntary EtOH consumption model where EtOH medium- and high-preferring rats were implanted with guide cannulae in the nAc. The animals received daily injections of acamprosate or 0.9% NaCl before accessing a bottle of 6% EtOH and a bottle of water. After 2 days, a microinjection of strychnine or vehicle preceded the daily systemic injection and bottle-access period.


RESULTS
Acamprosate, but not saline, decreased EtOH intake. Pretreatment with Ringer in the nAc did not influence EtOH intake in saline or acamprosate-treated animals. Pretreatment with strychnine had no effect on EtOH intake in saline-treated animals, whereas it completely reversed the EtOH intake-reducing effect of acamprosate.


CONCLUSIONS
Based on current and previous results, we suggest that acamprosate primarily interacts with accumbal GlyRs and secondarily with ventral tegmental nAChRs, in a similar manner to that previously observed with EtOH and taurine. The interaction between acamprosate and GlyRs does not only influence dopamine output in the nAc but also EtOH consumption, giving further support for our hypothesis that GlyRs are of importance in EtOH reinforcement.
Chau
Peipei
P
Addiction Biology Unit, Section of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden. peipei.chau@neuro.gu.se
Höifödt-Lidö
Helga
H
Löf
Elin
E
Söderpalm
Bo
B
Ericson
Mia
M
D000077443:Acamprosate; D000428:Alcohol Drinking / Q000378:metabolism* / Q000517:prevention & control*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism*; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism
D018009:Receptors, Glycine; D013654:Taurine; D000431:Ethanol; D000077443:Acamprosate; D004298:Dopamine