Reduced Nucleus Accumbens SK Channel Activity Enhances Alcohol Seeking During Abstinence

Neuron. 2010 Mar 11;65(5):682-94. doi: 10.1016/j.neuron.2010.02.015.

Abstract

The cellular mechanisms underlying pathological alcohol seeking remain poorly understood. Here, we show an enhancement of nucleus accumbens (NAcb) core action potential firing ex vivo after protracted abstinence from alcohol but not sucrose self-administration. Increased firing is associated with reduced small-conductance calcium-activated potassium channel (SK) currents and decreased SK3 but not SK2 subunit protein expression. Furthermore, SK activation ex vivo produces greater firing suppression in NAcb core neurons from alcohol- versus sucrose-abstinent rats. Accordingly, SK activation in the NAcb core significantly reduces alcohol but not sucrose seeking after abstinence. In contrast, NAcb shell and lateral dorsal striatal firing ex vivo are not altered after abstinence from alcohol, and SK activation in these regions has little effect on alcohol seeking. Thus, decreased NAcb core SK currents and increased excitability represents a critical mechanism that facilitates motivation to seek alcohol after abstinence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Analysis of Variance
  • Animals
  • Apamin / pharmacology
  • Behavior, Animal / drug effects
  • Benzimidazoles / pharmacology
  • Calcium Channel Agonists / pharmacology
  • Central Nervous System Depressants / administration & dosage
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ethanol / administration & dosage
  • Food Preferences / drug effects
  • Germinal Center Kinases
  • In Vitro Techniques
  • Male
  • Neurons / drug effects
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiopathology
  • Potassium Channels, Calcium-Activated / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Rats, Wistar
  • Reinforcement Schedule
  • Self Administration / methods
  • Small-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Sucrose / administration & dosage
  • Sweetening Agents / administration & dosage

Substances

  • Benzimidazoles
  • Calcium Channel Agonists
  • Central Nervous System Depressants
  • Germinal Center Kinases
  • Potassium Channels, Calcium-Activated
  • SK3 protein, rat
  • Small-Conductance Calcium-Activated Potassium Channels
  • Sweetening Agents
  • Apamin
  • Ethanol
  • Sucrose
  • Slk protein, rat
  • Protein-Serine-Threonine Kinases
  • 1-ethyl-2-benzimidazolinone