Influence of β-Endorphin on anxious behavior in mice: interaction with EtOH

Abstract

Rationale

The opioid peptide β-endorphin (β-E) is synthesized by the pro-opiomelanocortin gene in response to environmental stressors and alcohol administration and is implicated in the behavioral sequelae associated with these stimuli.

Objectives

We sought to determine the influence of β-E on the stress response by evaluating basal measures of anxiety as well as on EtOH-induced anxiolytic behavior using transgenic mice that differ with respect to β-E.

Methods

Anxious behavior was evaluated for male and female heterozygous, wild-type, and β-E knockout mice using the Light–Dark Box and Plus Maze assays. Subsequent tests evaluated behavior 20 min after administration of intraperitoneal saline or EtOH (0.5, 1.0, and 1.5 g/kg).

Results

We observed a direct relationship between β-E levels and the percentage of entries into open arms of the Plus Maze as well as the time spent in either the open arms or the light compartment of the Light–Dark box during basal conditions, suggesting that this peptide normally inhibits anxious behavior. However, mice lacking β-E demonstrated an exaggerated anxiolytic response to EtOH in these assays.

Conclusions

These data suggest that β-E moderates the response to stressful stimuli and supports the hypothesis that this peptide influences the behavioral effects of EtOH.

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Acknowledgements

The authors would like to acknowledge the foresight of Dr. John C. Crabbe at Oregon Health Sciences University that lead to this series of studies, the Psychology Department at Reed College, in Portland, OR, USA where the studies began and Christopher Smith, Gregory Cloonan, Amanda Lee, and Carmen Sanchez who assisted with experiments at Furman University.

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Correspondence to Judith E. Grisel.

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This publication was made possible by NIH Grant Numbers P20 RR-016461 from the National Center for Research Resources, AA13259 (through the INIA Stress Consortium) and AA13641 from the National Institute on Alcohol Abuse and Alcoholism.

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Grisel, J.E., Bartels, J.L., Allen, S.A. et al. Influence of β-Endorphin on anxious behavior in mice: interaction with EtOH. Psychopharmacology 200, 105–115 (2008). https://doi.org/10.1007/s00213-008-1161-4

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Keywords

  • Addiction
  • Ethanol
  • Anxiety
  • Opioids
  • Mice
  • Transgenic
  • Self-medication