Chronic ethanol exposure leads to divergent control of dopaminergic synapses in distinct target regions

Alcohol. 2008 May;42(3):179-90. doi: 10.1016/j.alcohol.2008.01.003. Epub 2008 Mar 20.


Neuroadaptations following chronic exposure to alcohol are hypothesized to play important roles in alcohol-induced alterations in behavior, in particular increased alcohol drinking and anxiety-like behavior. Dopaminergic signaling plays a key role in reward-related behavior, with evidence suggesting it undergoes modification following exposure to drugs of abuse. A large literature indicates an involvement of dopaminergic signaling in response to alcohol. Using a chronic inhalation model of ethanol exposure in mice, we have begun to investigate the effects of alcohol intake on dopaminergic signaling by examining protein levels of tyrosine hydroxylase and the dopamine transporter, as well as monoamine metabolites in three different target fields of three different dopaminergic nuclei. We have focused on the dorsal lateral bed nucleus of the stria terminalis because of the reported involvement of dorsal lateral bed nucleus of the stria terminalis dopamine in ethanol intake, and the nucleus accumbens and dorsal striatum because of their dense dopaminergic innervation. After either a chronic intermittent exposure or continuous exposure regimen, mice were killed, and tissue punches collected from the dorsal lateral bed nucleus of the stria terminalis, nucleus accumbens, and striatum for Western analysis. Strikingly, we found divergent regulation of tyrosine hydroxylase and dopamine transporter protein levels across these three regions that was dependent upon the means of exposure. These data thus suggest that distinct populations of catecholamine neurons may be differentially regulated by ethanol, and that ethanol and withdrawal interact to produce differential adaptations in these systems.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biogenic Monoamines / metabolism
  • Blotting, Western
  • Brain Chemistry / drug effects
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / blood
  • Central Nervous System Depressants / pharmacology*
  • Chromatography, High Pressure Liquid
  • Conditioning, Operant / drug effects
  • Corticosterone / blood
  • Dopamine / physiology*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Ethanol / administration & dosage
  • Ethanol / blood
  • Ethanol / pharmacology*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neostriatum / metabolism
  • Receptors, Dopamine / drug effects
  • Reinforcement Schedule
  • Substance Withdrawal Syndrome / prevention & control
  • Synapses / physiology*
  • Tyrosine 3-Monooxygenase / metabolism


  • Biogenic Monoamines
  • Central Nervous System Depressants
  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine
  • Ethanol
  • Tyrosine 3-Monooxygenase
  • Dopamine
  • Corticosterone