RT Journal Article
SR Electronic
T1 Ethanol Excitation of Dopaminergic Ventral Tegmental Area Neurons Is Blocked by Quinidine
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 437
OP 446
DO 10.1124/jpet.103.050963
VO 306
IS 2
A1 Sarah B. Appel
A1 Zhaoping Liu
A1 Maureen A. McElvain
A1 Mark S. Brodie
YR 2003
UL http://jpet.aspetjournals.org/content/306/2/437.abstract
AB The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are important for the reinforcing effects of ethanol. We have shown that ethanol directly excites DA VTA neurons and reduces the afterhyperpolarization (AHP) that follows spontaneous action potentials in these neurons. These data suggested that ethanol may be increasing the firing rate of DA VTA neurons by modulating currents that contribute to the AHP, either by reducing a K+ current or by increasing the inward current Ih. In the present study, different blockers of K+ channels and Ih were tested to determine whether any could prevent the ethanol excitation of DA VTA neurons. Extracellular single-unit recordings and whole-cell patch-clamp recordings were made from DA VTA neurons in brain slices from Fischer-344 rats and ethanol (40–120 mM) and channel blockers were applied in the bath. Ethanol excitation was not reduced by blockade of Ih with cesium (5 mM) or ZD7288 (30 μM), or by block of G-protein-coupled inwardly rectifying K+ channels with barium (500 μM). Tetraethylammonium (TEA) ion (2–10 mM), which blocks the large conductance calcium-dependent potassium K+ current and some types of delayed rectifier currents, had no effect on the ethanol-induced excitation. Interestingly, ethanol excitation of DA VTA neurons was blocked by quinidine (20–80 μM), a drug that blocks many types of delayed rectifier K+ channels, including some insensitive to TEA. This effect of quinidine was concentration-dependent and reversible. These results suggest that ethanol excites DA VTA neurons by reducing a quinidine-sensitive K+ current. The American Society for Pharmacology and Experimental Therapeutics