Reduced Nucleus Accumbens SK Channel Activity Enhances Alcohol Seeking during Abstinence

• DOI: 10.1016/j.neuron.2010.02.015
• Publication Date: 2010-03-11T09:56:13Z
• Authors: F. Woodward Hopf; M. Scott Bowers; Shao-Ju Chang; Billy T. Chen; Miguel Martin; Taban Seif; Saemi L. Cho; Kay Tye; Antonello Bonci
• Keywords: Male; Neuroscience(all); Action Potentials; In Vitro Techniques; Protein Serine-Threonine Kinases; MOLNEURO; Nucleus Accumbens; Germinal Center Kinases; Food Preferences; Potassium Channels, Calcium-Activated; 03 medical and health sciences; 0302 clinical medicine; Animals; Neurons; Analysis of Variance; Behavior, Animal; Dose-Response Relationship, Drug; Ethanol; Central Nervous System Depressants; Calcium Channel Agonists; Disease Models, Animal; Apamin; SIGNALING; Conditioning, Operant; Benzimidazoles

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.