Abstract
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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Kaltschmidt C, Kaltschmidt B, Neumann H, Wekerle H, Baeuerle PA (1994) Constitutive NF-kappa B activity in neurons. Mol Cell Bio 14:3981–3992
McDonald JW, Silverstein FS, Johnston MV (1988) Neurotoxicity of N-methyl-d-aspartate is markedly enhanced in developing rat central nervous system. Bra Rese 459:200–203
Stuckey DJ, Anthony DC, Lowe JP, Miller J et al (2005) Detection of the inhibitory neurotransmitter GABA in macrophages by magnetic resonance spectroscopy. J Leukoc Bio 78:393–400
Froestl W, Mickel SJ, von Sprecher G, Diel PJ et al (1995) Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists. J Med Chem 38:3313–3331
Cryan JF, Kaupmann K (2005) Don’t worry ‘B’ happy: a role for GABAB receptors in anxiety and depression. Trends Pharmacol Sci 26:36–43
Slattery DA, Desrayaud S, Cryan JF (2005) GABAB receptor antagonist-mediated antidepressant-like behavior is serotonin-dependent. J Pharm Eexp Thera 312:290–296
Romijn HJ, Hofman MA, Gramsbergen A (1991) At what age is the developing cerebral cortex of the rat comparable to that of the full-term newborn human baby? Early Hum Deve 26:61–67
Zahra K, Khan MA, Iqbal F (2015) Oral supplementation of Ocimum basilicum enhances the locomotory, exploratory and learning behavior of adult male albino mice. Neurolog Sci 36(1):73–78
Iqbal S, Ali M, Akbar A, Iqbal F (2014) Effects of dietary creatine supplementation for 8 weeks on neuromuscular coordination and learning in male albino mouse following neonatal hypoxic ischemic insult. Neurolog Sci. doi:10.1007/s10072-014-2041-9
Dutar P, Nicoll RA (1988) Pre and postsynaptic GABAB receptors in the hippocampus have different pharmacological properties. Neuron 1:585–591
Fukuda A, Mody I, Prince DA (1993) Differential ontogenesis of presynaptic and postsynaptic GABAB inhibition in rat somatosensory cortex. J Neurophy 70:448–452
Pitler TA, Alger BE (1994) Differences between presynaptic and postsynaptic GABAB mechanisms in rat hippocampal pyramidal cells. J Neurophy 72:2317–2327
Deisz RA (1999) The GABAB receptor antagonist CGP 55845A reduces presynaptic GABAB actions in neocortical neurons of the rat in vitro. Neurosciene 93:1241–1249
Gillani Q, Iqbal S, Arfa F, Khakwani S et al (2014) Effect of GABAB receptor antagonist (CGP 35348) on learning and memory in albino mice. The Sci Worl J. doi:10.1155/2014/983651
Gillani Q, Ali M, Iqbal F (2014) CGP 35348, GABAB receptor antagonist, has a potential to improve neuromuscular coordination and spatial learning in albino mouse following neonatal brain damage. Biomed Res Intern. doi:10.1155/2014/295215
Bettler B, Kaupmann K, Mosbacher J, Gassmann M (2004) Molecular structure and physiological functions of GABAB receptors. Physio Revi 84:835–867
Daenen EW, Van der Heyden JA, Kruse CG, Wolterink G, Van Ree JM (2001) Adaptation and habituation to an open field and responses to various stressful events in animals with neonatal lesions in the amygdala or ventral hippocampus. Bra Rese 918:153–165
Prior H, Schwegler H, Marashi V, Sachser N (2004) Exploration, emotionality, and hippocampal mossy fibers in nonaggressive AB/Gat and congenic highly aggressive mice. Hippocampus 14:135–140
Lubics A, Reglődi D, Tamás A, Kiss P et al (2005) Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxia-ischemia injury. Beha Brai Rese 157:157–165
Partyka A, Klodzinska A, Szewczyk B, Wieronska JM et al (2007) Effects of GABAB receptor ligands in rodent tests of anxiety-like behavior. J Pharma 59:757–762
Kleschevnikov AM, Belichenko PV, Faizi M, Jacobs LF, Htun K, Shamloo M, Mobley WC (2012) Deficits in cognition and synaptic plasticity in a mouse model of down syndrome ameliorated by GABAB receptor antagonists. J Neurosci 32(27):9217–9227
Ten VS, Wu EX, Tang H, Moore MB et al (2004) Late measures of brain injury after neonatal hypoxia ischemia in mice. Stroke 35:2183–2188
Isaacson JS, Solis JM, Nicoll RA (1993) Local and diffuse synaptic actions of GABA in the hippocampus. Neuron 10:165–175
Olpe H-R, Steinmann MW, Ferrat T, Pozza MF et al (1993) The actions of orally active GABAB receptor antagonists on GABAergic transmission in vivo and in vitro. Eu J Pharma 233:179–186
Brucato FH, Levin ED, Mott DD, Lewis DV, Wilson WA, Swartzwelder HS (1996) Hippocampal long-term potentiation and spatial learning in the rat: effects of GABA B receptor blockade. Neurosci 74:331–339
Getova D, Bowery NG, Spassov V (1996) Effects of GABAB receptor antagonists on learning and memory retention in a rat model of absence epilepsy. Pharm Rev Comm 8:141–143
Stäubli U, Scafidi J, Chun D (1999) GABAB receptor antagonism: facilitating effects on memory parallel on LTP induced by TBS but Not HFS. J Neurosci 19:4609–4615
Heese K, Otten U, Mathivet P, Raiteri M, Marescaux C, Bernasconi R (2000) GABA(B) receptor antagonists elevate both mRNA and protein levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) in brain and spinal cord of rats. Neuropharma 39:449–462
Jarvis S, Glinianaia SV, Arnaud C, Fauconnier J et al (2005) Case gender and severity in cerebral palsy varies with intrauterine growth. Arch Dis Child 90:474–479
Marlow N, Wolke D, Bracewell MA, Samara M (2005) Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 352:9–19
Zhu C, Xu F, Wang X, Shibata M et al (2006) Different apoptotic mechanisms are activated in male and female brains after neonatal hypoxia-ischaemia. J Neurochem 96:1016–1027
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This research project was funded by Higher Education commission (HEC) of Pakistan under 5000 indigenous Ph.D. Program.
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Gillani, Q.A., Akbar, A., Ali, M. et al. Gender-specific effects of CGP 55845, GABAB receptor antagonist, on neuromuscular coordination, learning and memory formation in albino mouse following neonatal hypoxia–ischemia insult. Neurol Sci 36, 961–969 (2015). https://doi.org/10.1007/s10072-015-2205-2
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DOI: https://doi.org/10.1007/s10072-015-2205-2