Ethanol-induced increases in dopamine extracellular concentration in rat nucleus accumbens are accounted for by increased release and not uptake inhibition.
We performed a quantitative microdialysis study to determine whether the increase in dialysate dopamine from the nucleus accumbens caused by intraperitoneal administration of ethanol (1 g/kg) was due to enhanced dopamine release or inhibition of dopamine uptake. The Lönnroth method (no net flux), adapted for transient conditions, was used to follow the time course of true extracellular dopamine concentrations in the nucleus accumbens simultaneously with the in vivo recovery of dopamine across the microdialysis probe. Separate groups of rats were perfused with artificial cerebral spinal fluid containing 0, 4, 8, or 12 nM dopamine for the entire experiment. Samples were taken every 10 min. Each rat received a saline or an ethanol injection. The concentration of dopamine gained by or lost from the probe was plotted as a function of the concentration of dopamine perfused into the probe for each time point. Linear regression was used to determine the slope of the line (in vivo recovery) and the x-intercept (point of no net flux) for each plot. The in vivo recovery did not significantly change over time for the saline- or the ethanol-injected rats. However, the point of no net flux (true extracellular concentration of dopamine) significantly increased after the ethanol injection from 9.4+/-0.4 nM (mean of six basal samples) to 13.2+/-1.8 nM, at the maximum, but did not change after the saline injection. On the basis of these results, it is suggested that the primary mechanism by which ethanol increases dialysate dopamine levels in the nucleus accumbens after intraperitoneal administration is by increasing dopamine release from the terminals, rather than by inhibiting the dopamine transporter.
Yim
H J
HJ
Department of Pharmacology, College of Pharmacy, University of Texas at Austin, 78712, USA.
Gonzales
R A
RA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism*; D007700:Kinetics; D016014:Linear Models; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D004298:Dopamine