Chronic inhibition of GABA synthesis in the bed nucleus of the stria terminalis elicits anxiety-like behavior

T. J. Sajdyk, P. L. Johnson, S. D. Fitz, A. Shekhar

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The current study tested the hypothesis that chronic loss of inhibitory GABAergic tone in the bed nucleus of the stria terminalis (BNST), a region implicated in anxiety behavior, results in generalized anxiety disorder-like behaviors without panic-like responses (i.e., tachycardia, hypertension and tachypnea) following panicogenic stimuli (e.g., sodium lactate infusions). To test this hypothesis, the GABA synthesis inhibitor L-allylglycine (L-AG) or its inactive isomer D-AG was chronically infused into the BNST of male rats via osmotic mini-pumps. L-AG, but not D-AG, treated rats had increased anxiety-like behavior as measured by social interaction (SI) and elevated-plus maze paradigms. Restoring GABAergic tone, with 100pmoles/100nl of muscimol (a GABAA receptor agonist), in the BNST of L-AG treated rats attenuated L-AG-induced anxiety-like behavior in the SI test. To assess panic-like states, L-AG treated rats were intravenously infused with 0.5 M sodium lactate, a panicogenic agent, prior to assessing SI and cardiorespiratory responses. L-AG decreased SI duration again; however, sodium lactate did not induce panic-like cardiorespiratory responses. These findings demonstrate that GABA inhibition in the BNST elicits anxiety-like behavior without increasing sensitivity to lactate, thus suggesting a behavioral profile similar to that of generalized anxiety-like behavior rather than that of panic.

Original languageEnglish (US)
Pages (from-to)633-641
Number of pages9
JournalJournal of Psychopharmacology
Volume22
Issue number6
DOIs
StatePublished - Aug 1 2008

Keywords

  • Amygdala
  • Anxiety disorder
  • BNST
  • Elevated-plus maze
  • Fear
  • Muscimol
  • Panic
  • Social interaction
  • Stria terminalis

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Neuroscience(all)

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