Abstract
Elevated sensitivity to the euphoric or stimulant effects of ethanol is associated with higher levels of alcohol use in some human populations. Midbrain dopamine neurons are thought to be important mediators of both ethanol reward and locomotor stimulation. Patch-clamp recordings were used to examine the electrical properties of dopamine neurons in a genetic model of heightened (FAST) and reduced (SLOW) sensitivity to the locomotor-activating effects of ethanol. Pacemaker firing of dopamine neurons was faster in FAST than SLOW mice, as was the current density through IH channels. Acute administration of ethanol accelerated the firing of dopamine neurons to a greater extent in recordings from FAST than SLOW mice. Dopamine neurons from FAST mice also exhibited reduced GABAA receptor-mediated synaptic input, compared with SLOW mice. The results suggest that dopamine neuron IH channels, firing rate, and GABAergic input may play a role in sensitivity to the locomotor activation observed at early time points after ethanol administration and could underlie differences in sensitivity to alcohol relevant to risk for alcohol abuse.
Footnotes
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This work was supported in part by the Department of Veterans Affairs; the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant AA10760]; and the National Institutes of Health National Institute on Drug Abuse [Grant DA21699].
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.108.146316.
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ABBREVIATIONS: VTA, ventral tegmental area; MK-801, dizocilpine maleate; G protein-coupled inwardly rectifying potassium channel; mIPSC, miniature inhibitory postsynaptic current; sIPSC, spontaneous inhibitory postsynaptic current; IPSC, inhibitory postsynaptic current; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ZD 7288, 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyridinium chloride; CGP 56999a, [3-{[1-R-(3-carboxyphenyl)ethyl]amino}-2-(S)-hydroxy-propyl]-cyclohexyl-methyl-phosphonic acid.
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↵1 Current affiliation: University of Texas Health Science Center at San Antonio, Department of Physiology, San Antonio, Texas.
- Received September 17, 2008.
- Accepted December 31, 2008.
- U.S. Government work not protected by U.S. copyright
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