TY - JOUR
T1 - Mice selectively bred for high- Or low-alcohol-induced locomotion exhibit differences in dopamine neuron function
AU - Beckstead, Michael J.
AU - Phillips, Tamara J.
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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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U2 - 10.1124/jpet.108.146316
DO - 10.1124/jpet.108.146316
M3 - Article
C2 - 19122113
AN - SCOPUS:63849308513
SN - 0022-3565
VL - 329
SP - 342
EP - 349
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -