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Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats

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Authors
Timić, Tamara
Divljaković, Jovana
Milinković, Marija M.
Rallapalli, Sundari
Cook, James M.
Savić, Miroslav
Conference object (Published version)
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Abstract
Objective : It is well known that benzodiazepine binding site ligands influence learning and memory and that the a5 subunit is significantly involved in cognition enhancement mediated by the negative modu- lation of GABAA receptor function. PWZ-029, a moderately selective a5GABA A receptor inverse agonist, improved learning in passive but not in active avoidance test, without effects on anxiety or muscle tone. The aim of this study was to investigate effects of PWZ-029 and DMCM, a non-selective inverse agonist, on learning ability and short- term memory in Morris water-maze (MWM) test. Methods : MWM test was conducted 20 minutes after in- traperitoneal administration of treatments (solvent, 5, 15 or 30 mg/kg PWZ-029 or 2 mg/kg DMCM) to male Wistar rats. The single-day MWM task consisted of 3 consecutive blocks of 4 trials lasting maxi- mally 60 s each and a probe trial. During spatial learning the platform was hidden in the middle of the NE quadrant. Results : Two-way AN...OVA with one repeated measure (block) and animals nested in treatment has shown that latency to find the plat- form, path efficiency and total distance travelled were on the control level for DMCM and all doses of PWZ-029. Factors block and treat- ment were significant only for latency to first entry to the NE quadrant [block effect : F(2,386)=10.50, p<0.001, treatment effect : F(4,31)=3.10, p<0.05]. Tukey’s post-hoc test revealed that animals treated with DMCM and 5 mg/kg of PWZ-029 had longer latency to first entry to the target quadrant than those treated with solvent (p=0.001, p<0.001, respectively). Probe trial performance did not differ signifi- cantly between treatments. Conclusion : These results suggest that neither non-selective nor b5 subunit-selective negative modulation of GABA A receptors is suf- ficient to enhance learning and short-term memory in the single-day MWM spatial task.

Source:
International Journal of Neuropsychopharmacology, 2012, 15, Supplement 1, 231-231
Publisher:
  • Oxford Univ Press, Oxford
Note:
  • 28th CINP World Congress of Neuropsychopharmacology, Stockholm, Sweden, 3–7 June 2012

DOI: 10.1017/S1461145712000508

ISSN: 1461-1457

WoS: 000209062500842

[ Google Scholar ]
Handle
https://hdl.handle.net/21.15107/rcub_farfar_1685
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1685
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - CONF
AU  - Timić, Tamara
AU  - Divljaković, Jovana
AU  - Milinković, Marija M.
AU  - Rallapalli, Sundari
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1685
AB  - Objective : It is well known that benzodiazepine binding site ligands
influence learning and memory and that the a5 subunit is significantly
involved in cognition enhancement mediated by the negative modu-
lation of GABAA receptor function. PWZ-029, a moderately selective
a5GABA A receptor inverse agonist, improved learning in passive but
not in active avoidance test, without effects on anxiety or muscle tone.
The aim of this study was to investigate effects of PWZ-029 and
DMCM, a non-selective inverse agonist, on learning ability and short-
term memory in Morris water-maze (MWM) test.
Methods : MWM test was conducted 20 minutes after in-
traperitoneal administration of treatments (solvent, 5, 15 or 30 mg/kg
PWZ-029 or 2 mg/kg DMCM) to male Wistar rats. The single-day
MWM task consisted of 3 consecutive blocks of 4 trials lasting maxi-
mally 60 s each and a probe trial. During spatial learning the platform
was hidden in the middle of the NE quadrant.
Results : Two-way ANOVA with one repeated measure (block) and
animals nested in treatment has shown that latency to find the plat-
form, path efficiency and total distance travelled were on the control
level for DMCM and all doses of PWZ-029. Factors block and treat-
ment were significant only for latency to first entry to the NE quadrant
[block effect : F(2,386)=10.50, p<0.001, treatment effect : F(4,31)=3.10,
p<0.05]. Tukey’s post-hoc test revealed that animals treated with
DMCM and 5 mg/kg of PWZ-029 had longer latency to first entry
to the target quadrant than those treated with solvent (p=0.001,
p<0.001, respectively). Probe trial performance did not differ signifi-
cantly between treatments.
Conclusion : These results suggest that neither non-selective nor b5
subunit-selective negative modulation of GABA A receptors is suf-
ficient to enhance learning and short-term memory in the single-day
MWM spatial task.
PB  - Oxford Univ Press, Oxford
C3  - International Journal of Neuropsychopharmacology
T1  - Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats
VL  - 15
IS  - Supplement 1
SP  - 231
EP  - 231
DO  - 10.1017/S1461145712000508
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1685
ER  - 
@conference{
author = "Timić, Tamara and Divljaković, Jovana and Milinković, Marija M. and Rallapalli, Sundari and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Objective : It is well known that benzodiazepine binding site ligands
influence learning and memory and that the a5 subunit is significantly
involved in cognition enhancement mediated by the negative modu-
lation of GABAA receptor function. PWZ-029, a moderately selective
a5GABA A receptor inverse agonist, improved learning in passive but
not in active avoidance test, without effects on anxiety or muscle tone.
The aim of this study was to investigate effects of PWZ-029 and
DMCM, a non-selective inverse agonist, on learning ability and short-
term memory in Morris water-maze (MWM) test.
Methods : MWM test was conducted 20 minutes after in-
traperitoneal administration of treatments (solvent, 5, 15 or 30 mg/kg
PWZ-029 or 2 mg/kg DMCM) to male Wistar rats. The single-day
MWM task consisted of 3 consecutive blocks of 4 trials lasting maxi-
mally 60 s each and a probe trial. During spatial learning the platform
was hidden in the middle of the NE quadrant.
Results : Two-way ANOVA with one repeated measure (block) and
animals nested in treatment has shown that latency to find the plat-
form, path efficiency and total distance travelled were on the control
level for DMCM and all doses of PWZ-029. Factors block and treat-
ment were significant only for latency to first entry to the NE quadrant
[block effect : F(2,386)=10.50, p<0.001, treatment effect : F(4,31)=3.10,
p<0.05]. Tukey’s post-hoc test revealed that animals treated with
DMCM and 5 mg/kg of PWZ-029 had longer latency to first entry
to the target quadrant than those treated with solvent (p=0.001,
p<0.001, respectively). Probe trial performance did not differ signifi-
cantly between treatments.
Conclusion : These results suggest that neither non-selective nor b5
subunit-selective negative modulation of GABA A receptors is suf-
ficient to enhance learning and short-term memory in the single-day
MWM spatial task.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Journal of Neuropsychopharmacology",
title = "Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats",
volume = "15",
number = "Supplement 1",
pages = "231-231",
doi = "10.1017/S1461145712000508",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1685"
}
Timić, T., Divljaković, J., Milinković, M. M., Rallapalli, S., Cook, J. M.,& Savić, M.. (2012). Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats. in International Journal of Neuropsychopharmacology
Oxford Univ Press, Oxford., 15(Supplement 1), 231-231.
https://doi.org/10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1685
Timić T, Divljaković J, Milinković MM, Rallapalli S, Cook JM, Savić M. Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats. in International Journal of Neuropsychopharmacology. 2012;15(Supplement 1):231-231.
doi:10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1685 .
Timić, Tamara, Divljaković, Jovana, Milinković, Marija M., Rallapalli, Sundari, Cook, James M., Savić, Miroslav, "Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats" in International Journal of Neuropsychopharmacology, 15, no. Supplement 1 (2012):231-231,
https://doi.org/10.1017/S1461145712000508 .,
https://hdl.handle.net/21.15107/rcub_farfar_1685 .

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