Journal article
The One-Two Punch of Alcoholism: Role of Central Amygdala Dynorphins/Kappa-Opioid Receptors
Biological psychiatry (1969), Vol.75(10), pp.774-782
05/15/2014
Handle:
https://hdl.handle.net/2376/109174
PMCID: PMC3749293
PMID: 23611261
Abstract
The dynorphin (DYN)/kappa-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacologic manipulations.
Male Wistar rats were trained to self-administer alcohol using operant behavioral strategies and subjected to intermittent alcohol vapor or air exposure. Changes in self-administration were assessed by pharmacologic challenges during acute withdrawal. In addition, 22-kHz ultrasonic vocalizations were utilized to measure negative affective-like states. Immunohistochemical techniques assessed DYN A peptide expression and [35S]GTPγS coupling assays were performed to assess KOR function.
Alcohol-dependent rats displayed increased alcohol self-administration, negative affective-like behavior, DYN A-like immunoreactivity, and KOR signaling in the amygdala compared with nondependent control rats. Site-specific infusions of a KOR antagonist selectively attenuated self-administration in dependent rats, whereas a mu-opioid receptor/delta-opioid receptor antagonist cocktail selectively reduced self-administration in nondependent rats. A mu-opioid receptor antagonist/partial KOR agonist attenuated self-administration in both cohorts.
Increased DYN A and increased KOR signaling could set the stage for a one-two punch during withdrawal that drives excessive alcohol consumption in alcohol dependence. Importantly, intracentral nucleus of the amygdala pharmacologic challenges functionally confirmed a DYN/KOR system involvement in the escalated alcohol self-administration. Together, the DYN/KOR system is heavily dysregulated in alcohol dependence and contributes to the excessive alcohol consumption during withdrawal.
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Details
- Title
- The One-Two Punch of Alcoholism: Role of Central Amygdala Dynorphins/Kappa-Opioid Receptors
- Creators
- Jessica L Kissler - Laboratory of Alcoholism and Addictions Neuroscience, Department of Psychology, Washington State University, Pullman, WashingtonSunil Sirohi - Laboratory of Alcoholism and Addictions Neuroscience, Department of Psychology, Washington State University, Pullman, WashingtonDaniel J Reis - Laboratory of Alcoholism and Addictions Neuroscience, Department of Psychology, Washington State University, Pullman, WashingtonHeiko T Jansen - Veterinary, Comparative Anatomy, Pharmacology and Physiology Department, Washington State University, Pullman, WashingtonRaymond M Quock - Department of Pharmaceutical Sciences, Washington State University, Pullman, WashingtonDaniel G Smith - Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, DenmarkBrendan M Walker - Laboratory of Alcoholism and Addictions Neuroscience, Department of Psychology, Washington State University, Pullman, Washington
- Publication Details
- Biological psychiatry (1969), Vol.75(10), pp.774-782
- Academic Unit
- Psychology, Department of; Integrative Physiology and Neuroscience, Department of
- Publisher
- Elsevier Inc
- Identifiers
- 99900547361901842
- Language
- English
- Resource Type
- Journal article