| Reference | 1. Pak J Pharm Sci. 2016 Sep;29(5):1503-1508.
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Effect of GABAB receptor antagonists (CGP 35348 and CGP 55845) on serum
interleukin 6 and 18 concentrations in albino mice following neonatal hypoxia
ischemia insult.
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Gillani Q(1), Ali M(2), Iqbal F(1).
<br>
Author information: <br>
(1)Institute of Pure and Applied Biology, Zoology Division, Bahauddin Zakariya
University, Multan, Pakistan.
(2)Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya
University Multan, Pakistan.
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Interleukin (IL) 6 and 18 plays an important role in inflammatory response
following hypoxia ischemia encephalopathy (HIE). Present study was designed to
demonstrate the effect of two GABAB receptor antagonists (CGP 35348 and 55845),
respectively, on the serum IL6 and IL 18 concentrations in albino mice. Albino
mice pups (of both genders) were subjected to Murine model of hypoxia-ischemia
encephalopathy on postnatal day 10 (right common carotid artery was ligated
followed by 8% hypoxia for 25 minutes). After neonatal brain damage and following
weaning, mice were divided in three groups, in gender specific manner, and fed on
normal rodent diet till they were 13 week old. At this time point, group 1
received intraperitonial saline solution (control group), group 2 was
supplemented with CGP 35348 (1mg/ml solvent/Kg body weight) and group 3 with CGP
55845 (1mg/ml solvent/Kg body weight), intraperitonially, for 12 days and IL 6
and 18 concentrations were determined in serum by ELISA. It was observed that CGP
35348 supplementation resulted in reduced interlukin-6 and interlukin-18
concentrations in male albino mice. While CGP 55845 supplementation increased
IL-6 and IL-18 concentrations in female albino mice following HIE. Our results
are indicating that GABAB receptor antagonist/’s supplementation affects IL
concentrations in albino mice in a gender specific manner following neonatal
brain damage and can be further explored for the treatments of hypoxia ischemia
associated neurological ailments.
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2. Neurol Sci. 2015 Jun;36(6):961-9. doi: 10.1007/s10072-015-2205-2. Epub 2015 Apr
7.
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Gender-specific effects of CGP 55845, GABAB receptor antagonist, on neuromuscular
coordination, learning and memory formation in albino mouse following neonatal
hypoxia-ischemia insult.
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Gillani QA(1), Akbar A, Ali M, Iqbal F.
<br>
Author information: <br>
(1)Zoology Division, Department of Zoology, Institute of Pure and Applied
Biology, Bahauddin Zakariya University, Multan, 60800, Pakistan.
<br>
GABAB receptor antagonists are experimentally proved as spatial memory enhancers
in mouse models but their role has not been described following hypoxic-ischemic
insult. 10-day-old albino mice were subjected to Murine model of hypoxia and
ischemia. Following brain damage, mice were fed on normal rodent diet till they
were 13 weeks old. At this time point, mice were divided into two groups. Group 1
received saline and group 2 received intraperitoneally CGP 55845 (1 mg/ml
solvent/Kg body weight) for 12 days. Behavioural observations were made during
rota rod, open field and Morris water maze test along with brain infarct
measurement in both CGP 55845 treated and untreated groups. It was observed that
application of GABAB receptor antagonist improved the over all motor function in
male and female albino mice but effects were more pronounced in males. In open
field, CGP 55845-treated female mice showed poor performance. CGP 55845 had no
significant effect on learning and memory formation during Morris water maze test
and also on brain infract size in both genders following hypoxia ischemia
encephalopathy. Effects of CGP 55845 can be further explored in a dose and
duration dependent manner to improve the learning and memory in albino mice
following neonatal brain damage.
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3. Neuropharmacology. 2008 Jul;55(1):47-54. doi: 10.1016/j.neuropharm.2008.04.010.
Epub 2008 Apr 23.
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Effects of subtype-selective group I mGluR antagonists on synchronous activity
induced by 4-aminopyridine/CGP 55845 in adult guinea pig hippocampal slices.
<br><br>
Salah A(1), Perkins KL.
<br>
Author information: <br>
(1)Program in Neural and Behavioral Science, State University of New York, SUNY
Downstate Medical Center, Box 29, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
<br>
Co-application of the convulsant 4-aminopyridine (4-AP) and the GABA(B) receptor
antagonist CGP 55845 to adult guinea pig hippocampal slices elicits giant
GABA-mediated postsynaptic potentials (GPSPs) and epileptiform discharges. Here
we tested the effects of the group I metabotropic glutamate receptor (mGluR)
subtype-selective antagonists LY 367385 (mGlu1, 100 microM), MPEP (mGlu5, 10
microM), and MTEP (mGlu5, 500 nM) on this synchronous activity.
Electrophysiological field recordings were performed in the CA3 region of
hippocampal slices from adult guinea pigs. The mGlu5 receptor antagonists
increased GPSP rate, but the mGlu1 receptor antagonist did not. This ability of
mGlu5 receptor antagonists to increase the rate of GPSPs indicates that enough
endogenous glutamate is released under these conditions to activate group I
mGluR; nevertheless, co-application of a mGlu1 receptor antagonist (LY 367385 or
JNJ 16259685) and MPEP did not decrease pre-existing epileptiform activity.
Furthermore, co-application of LY 367,385 and MPEP did not prevent the emergence
of epileptiform activity. When ionotropic glutamate receptor (iGluR) antagonists
were present, neither MPEP nor the group I mGluR agonist DHPG changed GPSP rate,
suggesting that pyramidal cell-to-interneuron iGluR-mediated synaptic connections
are involved in the rate change mechanism. In contrast to the lack of effect of
group I mGluR antagonists on epileptiform activity in the 4-AP/CGP 55845 model,
group I mGluR antagonists blocked the emergence of longer epileptiform events and
decreased the overall amount of synchronous activity in the GABA(A)
antagonist/4-AP model. In conclusion, in the 4-AP/CGP 55845 model, enough
glutamate was released to activate group I mGluRs and affect GPSP rate via mGlu5
receptors; however, this group I mGluR activation was not required for the
generation of the epileptiform activity.
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