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Handb Exp Pharmacol. 2018 Mar 11. doi: 10.1007/164_2018_100. [Epub ahead of print]

Contribution of Dynorphin and Orexin Neuropeptide Systems to the Motivational Effects of Alcohol.

Author information

1
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
2
Science and Technology Policy Fellowships, American Association for the Advancement of Science, Washington, DC, USA.
3
Department of Psychological and Brain Sciences, Neuroscience and Behavior Graduate Program, University of Massachusetts Amherst, Amherst, MA, USA.
4
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA. beckerh@musc.edu.
5
Charleston Alcohol Research Center, Medical University of South Carolina, Charleston, SC, USA. beckerh@musc.edu.
6
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA. beckerh@musc.edu.
7
Department of Veterans Affairs, Ralph H. Johnson VA Medical Center, Charleston, SC, USA. beckerh@musc.edu.

Abstract

Understanding the neural systems that drive alcohol motivation and are disrupted in alcohol use disorders is of critical importance in developing novel treatments. The dynorphin and orexin/hypocretin neuropeptide systems are particularly relevant with respect to alcohol use and misuse. Both systems are strongly associated with alcohol-seeking behaviors, particularly in cases of high levels of alcohol use as seen in dependence. Furthermore, both systems also play a role in stress and anxiety, indicating that disruption of these systems may underlie long-term homeostatic dysregulation seen in alcohol use disorders. These systems are also closely interrelated with one another - dynorphin/kappa opioid receptors and orexin/hypocretin receptors are found in similar regions and hypocretin/orexin neurons also express dynorphin - suggesting that these two systems may work together in the regulation of alcohol seeking and may be mutually disrupted in alcohol use disorders. This chapter reviews studies demonstrating a role for each of these systems in motivated behavior, with a focus on their roles in regulating alcohol-seeking and self-administration behaviors. Consideration is also given to evidence indicating that these neuropeptide systems may be viable targets for the development of potential treatments for alcohol use disorders.

KEYWORDS:

Alcohol; Dynorphin; Ethanol; Hypocretin; Kappa opioid receptor; Orexin

PMID:
29526023
DOI:
10.1007/164_2018_100

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