Antagonism by NOS inhibition of the behavioral effects of benzodiazepine and GABAA receptor agonists in the mouse elevated plus-maze

Geraldine S. Elfline, Emily M. Branda, Michael Babich, Raymond M. Quock

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Earlier we implicated nitric oxide (NO) in mediation of the behavioral effects of benzodiazepines. Since benzodiazepines work through facilitation of GABAergic inhibitory neurotransmission, this study was designed to determine whether the direct-acting γ-aminobutyric acidA (GABA A) receptor agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin- 3-ol) evokes behavioral effects similar to those of benzodiazepines and whether behavioral effects of THIP are also NO dependent. When challenged with either chlordiazepoxide or THIP in an elevated plus-maze paradigm, male NIH Swiss mice exhibited a dose-related increase in open-arm activity. The chlordiazepoxide- induced effects were sensitive to antagonism by a benzodiazepine antagonist, and the effects of THIP were blocked by a GABAA receptor antagonist. Pretreatment with the NO synthase (NOS) inhibitor L-NG-nitro arginine antagonized the effects of both chlordiazepoxide and THIP; similar pretreatment with the D-isomer, D-NG-nitro arginine, which is inactive as an NOS inhibitor, was without effect on chlordiazepoxide and THIP. These findings indicate that chlordiazepoxide and THIP evoke similar behavioral effects in mice in the elevated plus-maze through actions on different parts of the GABA A receptor, and that NO appears to play a key role in mediation of the behavioral effects of both chlordiazepoxide and THIP.

Original languageEnglish (US)
Pages (from-to)1419-1425
Number of pages7
JournalNeuropsychopharmacology
Volume29
Issue number8
DOIs
StatePublished - Aug 2004

Fingerprint

GABA-A Receptor Agonists
GABA-A Receptors
Nitric Oxide Synthase
Chlordiazepoxide
Benzodiazepines
Nitric Oxide
GABA-A Receptor Antagonists
gaboxadol
Nitroarginine
Synaptic Transmission
Arginine

Keywords

  • Anxiety
  • Benzodiazepines
  • Elevated plus-maze
  • GABA receptors
  • Nitric oxide

ASJC Scopus subject areas

  • Pharmacology

Cite this

Antagonism by NOS inhibition of the behavioral effects of benzodiazepine and GABAA receptor agonists in the mouse elevated plus-maze. / Elfline, Geraldine S.; Branda, Emily M.; Babich, Michael; Quock, Raymond M.

In: Neuropsychopharmacology, Vol. 29, No. 8, 08.2004, p. 1419-1425.

Research output: Contribution to journalArticle

Elfline, Geraldine S. ; Branda, Emily M. ; Babich, Michael ; Quock, Raymond M. / Antagonism by NOS inhibition of the behavioral effects of benzodiazepine and GABAA receptor agonists in the mouse elevated plus-maze. In: Neuropsychopharmacology. 2004 ; Vol. 29, No. 8. pp. 1419-1425.
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