title: Characterization of ethanol-induced dopamine elevation in the rat nucleus accumbens.
abstract: Ethanol-induced accumbal dopamine elevations have been linked to ethanol consumption. It is unclear, however, where along the mesolimbic dopamine system this effect is initiated and why the ethanol-induced dopamine elevations are transient, returning to pre-drug baseline before brain and blood ethanol levels decline. Using in vivo microdialysis, Experiment 1 investigated the effect of local ethanol application in the nucleus accumbens, the ventral tegmental area and the nucleus accumbens+the ventral tegmental area, on accumbal dopamine. Experiment 2 examined whether the rapid withdrawal of dopamine response to ethanol involves activation of GABA(A)-receptors, by analyzing the effect of accumbal co-perfusion of picrotoxin and ethanol. In Experiment 1, ethanol perfusion into the ventral tegmental area alone did not affect accumbal dopamine. Ethanol co-perfusion of one of the tested doses into the ventral tegmental+the nucleus accumbens produced higher dopamine levels than ethanol perfusion into the nucleus accumbens alone during 120-160 min following perfusion onset. In Experiment 2, accumbal ethanol perfusion caused a transient increase in nucleus accumbens dopamine. Co-perfusion of ethanol and picrotoxin produced a sustained dopamine elevation. These data support the hypothesis that the primary effect of ethanol on accumbal dopamine is in the nucleus accumbens, but that a secondary effect of nucleus accumbens ethanol perfusion, such as release of acetylcholine in the ventral tegmental area, enables ethanol to act as a nicotinic acetylcholine receptor co-agonist in this area. Moreover, recruitment of GABA(A)-receptor activity appears responsible for the second, declining phase with respect to dopamine levels following ethanol administration.
authors.affiliation: Institute of Neuroscience and Physiology, Section of Pharmacology, Sahlgrenska Academy, Göteborg University and Beroendekliniken, Sahlgrenska University Hospital, POB 410, SE-405 30, Gothenburg, Sweden. elin.lof@pharm.gu.se
authors.forename: Elin
authors.initials: E
authors.lastname: Löf
authors.forename: Mia
authors.initials: M
authors.lastname: Ericson
authors.forename: Rosita
authors.initials: R
authors.lastname: Stomberg
authors.forename: Bo
authors.initials: B
authors.lastname: Söderpalm
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D004298:Dopamine / Q000096:biosynthesis*; D000431:Ethanol / Q000008:administration & dosage*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D004298:Dopamine; D000431:Ethanol; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D011963:Receptors, GABA-A