The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats
2012
Autori
Milić, MarijaDivljaković, Jovana
Rallapalli, Sundari
van Linn, Michael
Timić, Tamara
Cook, James M.
Savić, Miroslav
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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
Ključne reči:
ataxia / grip strength / muscle relaxation / rat / rotarodIzvor:
Behavioural Pharmacology, 2012, 23, 2, 191-197Izdavač:
- Lippincott Williams & Wilkins, Philadelphia
Finansiranje / projekti:
DOI: 10.1097/FBP.0b013e3283512c85
ISSN: 0955-8810
PubMed: 22327019
WoS: 000301285400009
Scopus: 2-s2.0-84858708930
Institucija/grupa
PharmacyTY - 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 . .