Ethanol excitation of dopaminergic ventral tegmental area neurons is blocked by quinidine.
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 microM), or by block of G-protein-coupled inwardly rectifying K+ channels with barium (500 microM). 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 microM), 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.
Appel
Sarah B
SB
Department of Physiology and Biophysics (M/C 901), University of Illinois at Chicago, 835 S Wolcott Ave., Chicago, IL 60612-7342, USA. sappel@uic.edu
Liu
Zhaoping
Z
McElvain
Maureen A
MA
Brodie
Mark S
MS
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels; D011743:Pyrimidines / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011954:Receptors, Dopamine / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D002492:Central Nervous System Depressants; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D011743:Pyrimidines; D011954:Receptors, Dopamine; C082246:ICI D2788; D002586:Cesium; D001464:Barium; D000431:Ethanol; D019789:Tetraethylammonium; D011802:Quinidine; D004298:Dopamine