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The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats

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2012
1696.pdf (195.9Kb)
Authors
Milić, Marija
Divljaković, Jovana
Rallapalli, Sundari
van Linn, Michael
Timić, Tamara
Cook, James M.
Savić, Miroslav
Article (Published version)
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Abstract
Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of gamma-aminobutyric acid A (GABA(A)) receptors containing alpha(1) and alpha(5) subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the alpha(1)-selective agonist zolpidem, as well as nonselective, alpha(1)-subunit and alpha(5)-subunit-selective antagonists flumazenil, beta CCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10mg/kg) and beta CCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg.../kg) significantly decreased the grip strength. These effects of zolpidem were reversed by beta CCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that alpha(1) GABA(A) receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas alpha(5) GABA(A) receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia. Behavioural Pharmacology 23:191-197

Keywords:
ataxia / grip strength / muscle relaxation / rat / rotarod
Source:
Behavioural Pharmacology, 2012, 23, 2, 191-197
Publisher:
  • Lippincott Williams & Wilkins, Philadelphia
Funding / projects:
  • Behavioral ?ffects following repeated administration of newly synthesized ligands selective for distinct subtypes of GABAA receptor benzodiazepine binding site: comparison with standard psychopharmacologic drugs (RS-175076)

DOI: 10.1097/FBP.0b013e3283512c85

ISSN: 0955-8810

PubMed: 22327019

WoS: 000301285400009

Scopus: 2-s2.0-84858708930
[ Google Scholar ]
32
30
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1698
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Milić, Marija
AU  - Divljaković, Jovana
AU  - Rallapalli, Sundari
AU  - van Linn, Michael
AU  - Timić, Tamara
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1698
AB  - Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of gamma-aminobutyric acid A (GABA(A)) receptors containing alpha(1) and alpha(5) subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the alpha(1)-selective agonist zolpidem, as well as nonselective, alpha(1)-subunit and alpha(5)-subunit-selective antagonists flumazenil, beta CCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10mg/kg) and beta CCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg/kg) significantly decreased the grip strength. These effects of zolpidem were reversed by beta CCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that alpha(1) GABA(A) receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas alpha(5) GABA(A) receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia. Behavioural Pharmacology 23:191-197
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Behavioural Pharmacology
T1  - The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats
VL  - 23
IS  - 2
SP  - 191
EP  - 197
DO  - 10.1097/FBP.0b013e3283512c85
ER  - 
@article{
author = "Milić, Marija and Divljaković, Jovana and Rallapalli, Sundari and van Linn, Michael and Timić, Tamara and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of gamma-aminobutyric acid A (GABA(A)) receptors containing alpha(1) and alpha(5) subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the alpha(1)-selective agonist zolpidem, as well as nonselective, alpha(1)-subunit and alpha(5)-subunit-selective antagonists flumazenil, beta CCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10mg/kg) and beta CCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg/kg) significantly decreased the grip strength. These effects of zolpidem were reversed by beta CCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that alpha(1) GABA(A) receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas alpha(5) GABA(A) receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia. Behavioural Pharmacology 23:191-197",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Behavioural Pharmacology",
title = "The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats",
volume = "23",
number = "2",
pages = "191-197",
doi = "10.1097/FBP.0b013e3283512c85"
}
Milić, M., Divljaković, J., Rallapalli, S., van Linn, M., Timić, T., Cook, J. M.,& Savić, M.. (2012). The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats. in Behavioural Pharmacology
Lippincott Williams & Wilkins, Philadelphia., 23(2), 191-197.
https://doi.org/10.1097/FBP.0b013e3283512c85
Milić M, Divljaković J, Rallapalli S, van Linn M, Timić T, Cook JM, Savić M. The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats. in Behavioural Pharmacology. 2012;23(2):191-197.
doi:10.1097/FBP.0b013e3283512c85 .
Milić, Marija, Divljaković, Jovana, Rallapalli, Sundari, van Linn, Michael, Timić, Tamara, Cook, James M., Savić, Miroslav, "The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats" in Behavioural Pharmacology, 23, no. 2 (2012):191-197,
https://doi.org/10.1097/FBP.0b013e3283512c85 . .

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