Mice selectively bred for high- or low-alcohol-induced locomotion exhibit differences in dopamine neuron function.
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 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 locomotor activation observed at early time points after ethanol administration and could underlie differences in sensitivity to alcohol relevant to risk for alcohol abuse.
Beckstead
Michael J
MJ
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA. beckstead@uthscsa.edu.
Phillips
Tamara J
TJ
D000437:Alcoholism / Q000235:genetics / Q000523:psychology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000187:drug effects; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics*; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D013045:Species Specificity; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D054815:Cyclic Nucleotide-Gated Cation Channels; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D011963:Receptors, GABA-A; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D004298:Dopamine