Neurobiological mechanisms contributing to alcohol–stress–anxiety interactions

Silberman, Yuval; Bajo, Michal; Chappell, Ann M.; Christian, Daniel T.; Cruz, Maureen; Diaz, Marvin R.; Kash, Thomas; Lack, Anna K.; Messing, Robert O.; Siggins, George R.; Winder, Danny; Roberto, Marisa; McCool, Brian A.; Weiner, Jeff L.

doi:10.1016/j.alcohol.2009.01.002

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Volume 43, Issue 7 , Pages 509-519, November 2009

Neurobiological mechanisms contributing to alcohol–stress–anxiety interactions

Yuval Silberman
- Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Michal Bajo
- Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA
Ann M. Chappell
- Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
- Translational Center for the Neurobehavioral Study of Alcoholism, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Daniel T. Christian
- Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Maureen Cruz
- Committee on Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA
Marvin R. Diaz
- Neuroscience Training Program, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Thomas Kash
- Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA
Anna K. Lack
- Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Robert O. Messing
- Ernest Gallo Clinic and Research Center, Department of Neurology, University of California San Francisco, Emeryville, CA 94608, USA
George R. Siggins
- Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA
Danny Winder
- Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA
- Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA
- J.F. Kennedy Center for Research on Human Development, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA
Marisa Roberto
- Committee on Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA
- Pearson Center for Alcoholism and Addiction Research, The Scripps Research Institute, La Jolla, CA 92037, USA
Brian A. McCool
- Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
- Translational Center for the Neurobehavioral Study of Alcoholism, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Jeff L. Weiner
- Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
- Translational Center for the Neurobehavioral Study of Alcoholism, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
- Corresponding author. Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Tel.: +1-336-716-8692; fax: +1-336-716-8501.

Received 24 December 2008; accepted 22 January 2009.

Abstract

This article summarizes the proceedings of a symposium that was presented at a conference entitled “Alcoholism and Stress: A Framework for Future Treatment Strategies.” The conference was held in Volterra, Italy on May 6–9, 2008 and this symposium was chaired by Jeff L. Weiner. The overall goal of this session was to review recent findings that may shed new light on the neurobiological mechanisms that underlie the complex relationships between stress, anxiety, and alcoholism. Dr. Danny Winder described a novel interaction between D1 receptor activation and the corticotrophin-releasing factor (CRF) system that leads to an increase in glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Dr. Marisa Roberto presented recent data describing how protein kinase C epsilon, ethanol, and CRF interact to alter GABAergic inhibition in the central nucleus of the amygdala. Dr. Jeff Weiner presented recent advances in our understanding of inhibitory circuitry within the basolateral amygdala (BLA) and how acute ethanol exposure enhances GABAergic inhibition in these pathways. Finally, Dr. Brian McCool discussed recent findings on complementary glutamatergic and GABAergic adaptations to chronic ethanol exposure and withdrawal in the BLA. Collectively, these investigators have identified novel mechanisms through which neurotransmitter and neuropeptide systems interact to modulate synaptic activity in stress and anxiety circuits. Their studies have also begun to describe how acute and chronic ethanol exposure influence excitatory and inhibitory synaptic communication in these pathways. These findings point toward a number of novel neurobiological targets that may prove useful for the development of more effective treatment strategies for alcohol use disorders.

Keywords: Acute, Basolateral amygdala, Bed nucleus of the stria terminalis, Central nucleus of the amygdala, Chronic ethanol, CRF, Dopamine, GABA, Glutamate, Withdrawal