Mice selectively bred for high- Or low-alcohol-induced locomotion exhibit differences in dopamine neuron function

Michael J. Beckstead, Tamara Phillips

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 loco- motor-activating effects of ethanol. Pacemaker firing of dopamine neurons was faster in FAST than SLOW mice, as was the current density through I H 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 GABA A receptor-mediated synaptic input, compared with SLOW mice. The results suggest that dopamine neuron I H channels, firing rate, and GABAergic input may play a role in sensitivity to the loco- motor activation observed at early time points after ethanol administration and could underlie differences in sensitivity to alcohol relevant to risk for alcohol abuse.

Original languageEnglish (US)
Pages (from-to)342-349
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume329
Issue number1
DOIs
StatePublished - Apr 2009

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Dopaminergic Neurons
Locomotion
Alcohols
Ethanol
Genetic Models
GABA-A Receptors
Mesencephalon
Reward
Alcoholism
Population

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

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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 loco- motor-activating effects of ethanol. Pacemaker firing of dopamine neurons was faster in FAST than SLOW mice, as was the current density through I H 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 GABA A receptor-mediated synaptic input, compared with SLOW mice. The results suggest that dopamine neuron I H channels, firing rate, and GABAergic input may play a role in sensitivity to the loco- motor activation observed at early time points after ethanol administration and could underlie differences in sensitivity to alcohol relevant to risk for alcohol abuse.",
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