The shell of the nucleus accumbens has a higher dopamine response compared with the core after non-contingent intravenous ethanol administration.
Dopamine increases in the nucleus accumbens after ethanol administration in rats, but the contributions of the core and shell subregions to this response are unclear. The goal of this study was to determine the effect of various doses of i.v. ethanol infusions on dopamine in these two subregions of the nucleus accumbens. Male Long-Evans rats were infused with either acute i.v. ethanol (0.5, 1.0, 1.5 g/kg), repeated i.v. ethanol (four 1.0 g/kg infusions resulting in a cumulative dose of 4.0 g/kg), or saline as a control for each condition. Dopamine and ethanol were measured in dialysate samples from each experiment. The in vivo extraction fraction for ethanol of probes was determined using i.v. 4-methylpyrazole, and was used to estimate peak brain ethanol concentrations after the infusions. The peak brain ethanol concentrations after the 0.5, 1.0 and 1.5 g/kg ethanol infusions were estimated to be 20, 49 and 57 mM, respectively. A significant dopamine increase was observed for the 0.5 g/kg ethanol group when collapsed across subregions. However, both the 1.0 g/kg and 1.5 g/kg ethanol infusions produced significant increases in dopamine levels in the shell that were significantly higher than those in the core. An ethanol dose-response effect on dopamine in the shell was observed when saline controls, 0.5, 1.0, and 1.5 g/kg groups were compared. For the cumulative-dosing study, the first, second, and fourth infusions resulted in significant increases in dopamine in the shell. However, these responses were not significantly different from one another. The results of this study show that the shell has a stronger response than the core to i.v. ethanol, that dopamine in the shell increases in a dose-dependent manner between 0.5-1.0 g/kg doses, but that the response to higher ethanol doses reaches a plateau.
College of Pharmacy, Department of Pharmacology, The University of Texas at Austin, 1 University Station A1915, Austin, TX 78712, USA.
E C
EC
Howard
C J
CJ
Schier
J S
JS
Wetzel
C L
CL
Duvauchelle
R A
RA
Gonzales
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077604:Fomepizole; D007262:Infusions, Intravenous; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D004298:Dopamine