Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors

Jessica L Kissler; Brendan M Walker

doi:10.1038/npp.2015.183

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Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors

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Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors

Jessica L Kissler and Brendan M Walker

Neuropsychopharmacology (New York, N.Y.), Vol.41(2), pp.560-567

01/2016

DOI: https://doi.org/10.1038/npp.2015.183

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https://hdl.handle.net/2376/108554

PMCID: PMC5130131

PMID: 26105136

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Abstract

Naltrexone - analogs & derivatives

Rats, Wistar

Conditioning, Operant - physiology

Ethanol - administration & dosage

Substance Withdrawal Syndrome - drug therapy

Male

Dose-Response Relationship, Drug

Motivation - drug effects

Naltrexone - pharmacology

Self Administration

Substance Withdrawal Syndrome - metabolism

Conditioning, Operant - drug effects

Alcoholism - psychology

Disease Models, Animal

Receptors, Opioid, kappa - antagonists & inhibitors

Receptors, Opioid, kappa - metabolism

Administration, Intranasal

Animals

Motivation - physiology

Narcotic Antagonists - pharmacology

Alcoholism - metabolism

Central Nervous System Depressants - administration & dosage

Alcoholism - drug therapy

Central Amygdaloid Nucleus - metabolism

Substance Withdrawal Syndrome - psychology

Chronic intermittent alcohol vapor exposure leads to increased dynorphin (DYN) A-like peptide expression and heightened kappa-opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA) and these neuroadaptive responses differentiate alcohol-dependent from non-dependent phenotypes. Important for therapeutic development efforts is understanding the nature of the stimulus that drives dependence-like phenotypes such as escalated alcohol self-administration. Accordingly, the present study examined the impact of intra-CeA KOR antagonism on escalated operant alcohol self-administration and physiological withdrawal symptoms during acute withdrawal and protracted abstinence in rats previously exposed to chronic intermittent alcohol vapor. Following operant training, rats were implanted with intra-CeA guide cannula and exposed to long-term intermittent alcohol vapor exposure that resulted in escalated alcohol self-administration and elevated physiological withdrawal signs during acute withdrawal. Animals received intra-CeA infusions of the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 2, 4, or 6 μg) prior to operant alcohol self-administration sessions and physiological withdrawal assessment during acute withdrawal and protracted abstinence. The results indicated that site-specific KOR antagonism in the CeA ameliorated escalated alcohol self-administration during both acute withdrawal and protracted abstinence test sessions, whereas KOR antagonism had no effect on physiological withdrawal scores at either time point. These results dissociate escalated alcohol self-administration from physiological withdrawal symptoms in relation to KOR signaling in the CeA and help clarify the nature of the stimulus that drives escalated alcohol self-administration during acute withdrawal and protracted abstinence.

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Title: Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors
Creators: Jessica L Kissler - Laboratory of Alcoholism and Addictions Neuroscience, Translational Addiction Research Center, Department of Psychology, Washington State University, Pullman, WA, USA
Brendan M Walker - Laboratory of Alcoholism and Addictions Neuroscience, Translational Addiction Research Center, Department of Psychology, Washington State University, Pullman, WA, USA
Publication Details: Neuropsychopharmacology (New York, N.Y.), Vol.41(2), pp.560-567
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: England
Grant note: R01AA020394 / NIAAA NIH HHS R01 AA020394 / NIAAA NIH HHS
Identifiers: 99900546858601842
Language: English
Resource Type: Journal article