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 language | English (US) |
|---|---|
| Pages (from-to) | 1419-1425 |
| Number of pages | 7 |
| Journal | Neuropsychopharmacology |
| Volume | 29 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2004 |
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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 journal › Article
}
TY - JOUR
T1 - Antagonism by NOS inhibition of the behavioral effects of benzodiazepine and GABAA receptor agonists in the mouse elevated plus-maze
AU - Elfline, Geraldine S.
AU - Branda, Emily M.
AU - Babich, Michael
AU - Quock, Raymond M.
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
KW - Anxiety
KW - Benzodiazepines
KW - Elevated plus-maze
KW - GABA receptors
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=3242815315&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3242815315&partnerID=8YFLogxK
U2 - 10.1038/sj.npp.1300437
DO - 10.1038/sj.npp.1300437
M3 - Article
C2 - 15136793
AN - SCOPUS:3242815315
VL - 29
SP - 1419
EP - 1425
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 8
ER -