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J Neurophysiol (July 9, 2008). doi:10.1152/jn.00994.2007
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Submitted on September 5, 2007
Accepted on July 5, 2008

Ethanol effects on dopaminergic ventral tegmental area neurons during block of Ih: Involvement of barium-sensitive potassium currents

John McDaid1, Maureen A. McElvain1, and Mark S. Brodie1*

1 Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois, United States

* To whom correspondence should be addressed. E-mail: mbrodie{at}uic.edu.

The dopaminergic neurons of the ventral tegmental area (DA VTA neurons) are important for the rewarding and reinforcing properties of drugs of abuse, including ethanol. Ethanol increases the firing frequency of DA VTA neurons from rats and mice. Due to a recent report on block of ethanol excitation in mouse DA VTA neurons with ZD7288, a selective blocker of the hyperpolarization-activated cationic current Ih, we examined the effect of ZD7288 on ethanol excitation in DA VTA neurons from C57Bl/6J and DBA/2J mice, and Fisher 344 rats. Ethanol (80mM) caused only increases in firing rate in mouse DA VTA neurons in the absence of ZD7288, but in the presence of ZD7288 (30µM), ethanol produced a more transient excitation followed by a decrease of firing. This same biphasic phenomenon was observed in DA VTA neurons from rats in the presence of ZD7288 only at very high ethanol concentrations (160-240mM), but not at lower pharmacologically-relevant concentrations. The longer latency ethanol-induced inhibition was not observed in DA VTA neurons from mice or rats in the presence of barium (100µM), which blocks g-protein-linked potassium channels (GIRKs) and other inwardly-rectifying potassium channels. Ethanol may have a direct effect to increase an inhibitory potassium conductance, but this effect of ethanol can only decrease the firing rate if Ih is blocked.




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