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

Research output: Contribution to journalArticle

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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.

LanguageEnglish (US)
Pages423-434
Number of pages12
JournalAddiction Biology
Volume22
Issue number2
DOIs
StatePublished - Mar 1 2017

Fingerprint

Compulsive Behavior
Punishment
Prefrontal Cortex
Drug and Narcotic Control
Reward
Alcoholism
Reverse Transcription
Rodentia
Ethanol
Air
Gene Expression
Food
Polymerase Chain Reaction
Brain
aspartic acid receptor

Keywords

  • Addiction
  • alcohol
  • CIE
  • mouse
  • NMDAR
  • orbitofrontal cortex

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

Radke, A. K., Jury, N. J., Kocharian, A., Marcinkiewcz, C. A., Lowery-Gionta, E. G., Pleil, K. E., ... Holmes, A. (2017). Chronic EtOH effects on putative measures of compulsive behavior in mice. Addiction Biology, 22(2), 423-434. DOI: 10.1111/adb.12342

Chronic EtOH effects on putative measures of compulsive behavior in mice. / Radke, Anna K.; Jury, Nicholas J.; Kocharian, Adrina; Marcinkiewcz, Catherine A.; Lowery-Gionta, Emily G.; Pleil, Kristen E.; McElligott, Zoe A.; McKlveen, Jessica M.; Kash, Thomas L.; Holmes, Andrew.

In: Addiction Biology, Vol. 22, No. 2, 01.03.2017, p. 423-434.

Research output: Contribution to journalArticle

Radke, AK, Jury, NJ, Kocharian, A, Marcinkiewcz, CA, Lowery-Gionta, EG, Pleil, KE, McElligott, ZA, McKlveen, JM, Kash, TL & Holmes, A 2017, 'Chronic EtOH effects on putative measures of compulsive behavior in mice' Addiction Biology, vol. 22, no. 2, pp. 423-434. DOI: 10.1111/adb.12342
Radke AK, Jury NJ, Kocharian A, Marcinkiewcz CA, Lowery-Gionta EG, Pleil KE et al. Chronic EtOH effects on putative measures of compulsive behavior in mice. Addiction Biology. 2017 Mar 1;22(2):423-434. Available from, DOI: 10.1111/adb.12342
Radke, Anna K. ; Jury, Nicholas J. ; Kocharian, Adrina ; Marcinkiewcz, Catherine A. ; Lowery-Gionta, Emily G. ; Pleil, Kristen E. ; McElligott, Zoe A. ; McKlveen, Jessica M. ; Kash, Thomas L. ; Holmes, Andrew. / Chronic EtOH effects on putative measures of compulsive behavior in mice. In: Addiction Biology. 2017 ; Vol. 22, No. 2. pp. 423-434
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