Amygdala Arginine Vasopressin Modulates Chronic Ethanol Withdrawal Anxiety-Like Behavior in the Social Interaction Task

Kathryn M. Harper, Darin J. Knapp, Ryan K. Butler, Cory A. Cook, Hugh E. Criswell, Garret D. Stuber, George R. Breese

Research output: Contribution to journalArticle

Abstract

Background: Chronic ethanol (EtOH) exposure induces neurobehavioral maladaptations in the brain though the precise changes have not been fully explored. The central nucleus of the amygdala (CEA) regulates anxiety-like behavior induced by withdrawal from chronic intermittent EtOH (CIE) exposure, and the arginine vasopressin (AVP) system within the CEA regulates many anxiety-like behaviors. Thus, adaptations occur in the CEA AVP system due to chronic EtOH exposure, which lead to anxiety-like behaviors in rats. Methods: Chronic exposure to a low-dose EtOH (4.5% wt/vol) induces anxiety-like behavior in rats. Wistar or Sprague Dawley rats were exposed to a modified CIE or CIE, while intra-CEA microinjections of AVP or a V1b receptor antagonist were used to elicit or block withdrawal-induced anxiety. Additionally, AVP microinjections into the CEA were given 24 hours following 15 days of continuous high-dose EtOH (7% wt/vol), a time period when rats no longer express anxiety. Chemogenetics was also used to activate the basolateral amygdala (BLA) or deactivate the dorsal periaqueductal gray=(dm/dlPAG) therefore PAG=periaqueductal gray to elicit or block withdrawal-induced anxiety. Results: AVP microinjected into the CEA in lieu of exposure to the first 2 cycles of CIE was sufficient to induce anxiety-like behavior in these commonly used rat strains. The V1b receptor antagonist, but not an oxytocin receptor agonist, into the CEA during the first 2 withdrawal cycles suppressed anxiety. However, activation of the BLA in lieu of exposure to the first 2 cycles of CIE was insufficient to induce anxiety-like behavior. AVP microinjection into the CEA 24 hours into withdrawal reelicited anxiety-like behavior, and deactivation of the dm/dlPAG reduced this effect of CEA AVP. Conclusions: Taken together, this study demonstrates a role of CEA AVP and a CEA-dm/dlPAG circuit in the development of anxiety induced by CIE. Such information is valuable for identifying novel therapeutic targets for alcohol- and anxiety-associated disorders.

Original languageEnglish (US)
Pages (from-to)2134-2143
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume43
Issue number10
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

Fingerprint

Arginine Vasopressin
Interpersonal Relations
Amygdala
Ethanol
Anxiety
Rats
Microinjections
Periaqueductal Gray
Oxytocin Receptors
Brain
Chemical activation
Alcohols
Anxiety Disorders
Sprague Dawley Rats
Networks (circuits)

Keywords

  • Alcohol
  • Alcohol Withdrawal–Induced Anxiety
  • Basolateral Amygdala
  • Central Nucleus of the Amygdala
  • Chemogenetics
  • Dorsal Periaqueductal Gray

ASJC Scopus subject areas

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

Cite this

Amygdala Arginine Vasopressin Modulates Chronic Ethanol Withdrawal Anxiety-Like Behavior in the Social Interaction Task. / Harper, Kathryn M.; Knapp, Darin J.; Butler, Ryan K.; Cook, Cory A.; Criswell, Hugh E.; Stuber, Garret D.; Breese, George R.

In: Alcoholism: Clinical and Experimental Research, Vol. 43, No. 10, 01.10.2019, p. 2134-2143.

Research output: Contribution to journalArticle

Harper, Kathryn M. ; Knapp, Darin J. ; Butler, Ryan K. ; Cook, Cory A. ; Criswell, Hugh E. ; Stuber, Garret D. ; Breese, George R. / Amygdala Arginine Vasopressin Modulates Chronic Ethanol Withdrawal Anxiety-Like Behavior in the Social Interaction Task. In: Alcoholism: Clinical and Experimental Research. 2019 ; Vol. 43, No. 10. pp. 2134-2143.
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