Characterization of ethanol-induced dopamine elevation in the rat nucleus accumbens

• Published in: European journal of pharmacology 2007-01, Vol.555 (2), p.148-155
• Main Authors: Löf, Elin, Ericson, Mia, Stomberg, Rosita, Söderpalm, Bo
• Format: Article
• Language: English
• Subjects: Addiction; administration & dosage; Animals; antagonists & inhibitors; Beroendelära; Biological and medical sciences; biosynthesis; Central Nervous System Depressants; Central Nervous System Depressants - administration & dosage; Dopamine; Dopamine - biosynthesis; drug effects; Ethanol; Ethanol - administration & dosage; Farmakologi och toxikologi; GABA; GABA Antagonists; GABA Antagonists - pharmacology; GABA-A; GABA-A Receptor Antagonists; Male; Medical sciences; metabolism; Microdialysis; Neurosciences; Neurovetenskaper; Nucleus Accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; pharmacology; Pharmacology and Toxicology; Pharmacology. Drug treatments; Picrotoxin; Picrotoxin - pharmacology; Rat; Rats; Rats, Wistar; Receptors; Receptors, GABA-A - metabolism; Substance Abuse; Ventral Tegmental Area; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - metabolism; Wistar
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.10.055

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.