Chronic EtOH effects on putative measures of compulsive behavior in mice

Anna K Radke; Nicholas J Jury; Adrina Kocharian; Catherine A Marcinkiewcz; Emily G Lowery-Gionta; Kristen E Pleil; Zoe A McElligott; Jessica M McKlveen; Thomas L Kash; Andrew Holmes

doi:10.1111/adb.12342

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Chronic EtOH effects on putative measures of compulsive behavior in mice

Journal article

Peer reviewed

Chronic EtOH effects on putative measures of compulsive behavior in mice

Anna K Radke, Nicholas J Jury, Adrina Kocharian, Catherine A Marcinkiewcz, Emily G Lowery-Gionta, Kristen E Pleil, Zoe A McElligott, Jessica M McKlveen, Thomas L Kash and Andrew Holmes

Addiction biology, Vol.22(2), pp.423-434

03/2017

DOI: 10.1111/adb.12342

PMCID: PMC4916036

PMID: 26687341

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Abstract

Addictions, including alcohol use disorders, are characterized by the loss of control over drug seeking and consumption, but the neural circuits and signaling mechanisms responsible for the transition from controlled use to uncontrolled abuse remain incompletely understood. Prior studies have shown that 'compulsive-like' behaviors in rodents, for example, persistent responding for ethanol (EtOH) despite punishment, are increased after chronic exposure to EtOH. The main goal of the current study was to assess the effects of chronic intermittent EtOH (CIE) exposure on multiple, putative measures of compulsive-like EtOH seeking in C57BL/6 J mice. Mice were exposed to two or four weekly cycles of CIE and then, post-withdrawal, tested for progressive ratio responding for EtOH, sustained responding during signaled EtOH unavailability and (footshock) punished suppression of responding for EtOH. Results showed that mice exposed to CIE exhibited attenuated suppression of EtOH seeking during punishment, as compared with air-exposed controls. By contrast, CIE exposure affected neither punished food reward-seeking behavior, nor other putative measures of compulsive-like EtOH seeking. Ex vivo reverse transcription polymerase chain reaction analysis of brain tissue found reduced sensitivity to punished EtOH seeking after CIE exposure was accompanied by a significant increase in gene expression of the GluN1 and GluN2A subunits of the N-methyl-d-aspartate receptor, specifically in the medial orbitofrontal cortex. Moreover, slice electrophysiological analysis revealed increased N-methyl-d-aspartate receptor-mediated currents in the orbitofrontal cortex after CIE exposure in test-naïve mice. Collectively, the current findings add to the growing body of evidence demonstrating that chronic exposure to EtOH fosters resistance to punished EtOH seeking in association with adaptations in cortical glutamatergic transmission.

Punishment

Receptors, N-Methyl-D-Aspartate - drug effects

Mice, Inbred C57BL

Compulsive Behavior - genetics

Ethanol - administration & dosage

Male

Reverse Transcriptase Polymerase Chain Reaction

Nerve Tissue Proteins - drug effects

Nerve Tissue Proteins - genetics

Drug-Seeking Behavior - drug effects

Receptors, N-Methyl-D-Aspartate - genetics

Brain - drug effects

Brain - metabolism

Central Nervous System Depressants - pharmacology

Ethanol - pharmacology

Animals

Prefrontal Cortex - drug effects

Central Nervous System Depressants - administration & dosage

Prefrontal Cortex - metabolism

Behavior, Animal - drug effects

Mice

Reward

Food

Details

Title: Subtitle: Chronic EtOH effects on putative measures of compulsive behavior in mice
Creators: Anna K Radke - Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
Nicholas J Jury - Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
Adrina Kocharian - Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
Catherine A Marcinkiewcz - Bowles Center for Alcohol Studies and Department of Pharmacology, UNC Chapel Hill School of Medicine, Chapel Hill, NC, USA
Emily G Lowery-Gionta - Bowles Center for Alcohol Studies and Department of Pharmacology, UNC Chapel Hill School of Medicine, Chapel Hill, NC, USA
Kristen E Pleil - Bowles Center for Alcohol Studies and Department of Pharmacology, UNC Chapel Hill School of Medicine, Chapel Hill, NC, USA
Zoe A McElligott - Bowles Center for Alcohol Studies and Department of Psychiatry, UNC Chapel Hill School of Medicine, Chapel Hill, NC, USA
Jessica M McKlveen - Bowles Center for Alcohol Studies and Department of Pharmacology, UNC Chapel Hill School of Medicine, Chapel Hill, NC, USA
Thomas L Kash - Bowles Center for Alcohol Studies and Department of Pharmacology, UNC Chapel Hill School of Medicine, Chapel Hill, NC, USA
Andrew Holmes - Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
Resource Type: Journal article
Publication Details: Addiction biology, Vol.22(2), pp.423-434
DOI: 10.1111/adb.12342
PMID: 26687341
PMCID: PMC4916036
NLM abbreviation: Addict Biol
ISSN: 1355-6215
eISSN: 1369-1600
Publisher: Wiley; United States
Grant note: K01 AA023555 / NIAAA NIH HHS K99 AA023559 / NIAAA NIH HHS U01 AA020911 / NIAAA NIH HHS Z99 AA999999 / Intramural NIH HHS R01 AA019454 / NIAAA NIH HHS R00 AA023559 / NIAAA NIH HHS T32 AA007573 / NIAAA NIH HHS U24 AA025475 / NIAAA NIH HHS P50 AA011605 / NIAAA NIH HHS P60 AA011605 / NIAAA NIH HHS F32 AA022549 / NIAAA NIH HHS
Language: English
Date published: 03/2017
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984040386702771

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