CGP 35348, GABA_BReceptor Antagonist, Has a Potential to Improve Neuromuscular Coordination and Spatial Learning in Albino Mouse following Neonatal Brain Damage

Abstract

To study the effect of CGP 35348 on learning and memory in albino mice following hypoxia ischemia insult, 10 days old albino mice were subjected to right common carotid artery ligation followed by 8% hypoxia for 25 minutes. Following brain damage, mice were fed on normal rodent diet till they were 13 week old. At this time point, mice were divided into two groups. Group 1 received saline and group 2 intrapertoneally CGP 35348 (1 mg/mL solvent/Kg body weight) for 12 days. A battery of tests used to assess long term neurofunction (Morris water maze, Rota rod and open field) along with brain infarct measurement. Overall CGP 35348 has improved the motor function in male and female albino mice but effects were more pronounced in female albino mice. In open field, CGP 35348 treated female albino mice had demonstrated poor exploratory behavior. During Morris water maze test, gender specific effects were observed as CGP 35348 had improved spatial learning and memory and swimming speed in male albino mice but had no effect in female albino mice following hypoxia ischemia encephalopathy (HIE). We concluded that GABAB receptor antagonists CGP 35348 can be used to improve gender based spatial memory.

Sex‐dependent consequences of neonatal brain hypoxia‐ischemia in the rat

“…In the footprints and wire‐suspension tests, HI males have shorter step length and toe distance in the contralateral limbs (Huang et al, ) and are less successful at grasping the dowel with hindlimbs and hanging on it (Waddell et al, ). With regard to balance and motor coordination deficits in the rota‐rod task, some authors have found no significant differences between males and females after the HI insult (Pimentel‐Coelho et al, ; Uluc et al, ; Gillani et al, ; Peterson et al, ). Nevertheless, HI males did not exhibit significant improvement in sensorimotor behavioral tests after different neuroprotective treatments compared with HI females (Bona et al, ; Thoresen et al, ; Fan et al, ; Pimentel‐Coelho et al, ; Smith et al, ).…”

GABAergic system and chloride cotransporters as potential therapeutic targets to mitigate cell death in ischemia

“…Although gabapentin reduces seizures and brain atrophy after the ischemic event, males had an even greater reduction in seizures and brain atrophy with higher doses of gabapentin than did females (Traa et al, 2008). CGP35348, a GABA B receptor antagonist, improves motor performance in rodents, but only in females (Gillani et al, 2014(Gillani et al, , 2015. Finally, age of treatment is critical to the therapeutic potential of GABA, as it must coincide with the CNS developmental stage that GABA promotes, via GABA A activation, an inhibitory response instead of excitatory (Nuñez et al, 2003a(Nuñez et al, , 2003b.…”

The Roles of GABA in Ischemia-Reperfusion Injury in the Central Nervous System and Peripheral Organs

“…Therefore, activating GABA A receptor may aggregate the I/R injury in the neocortex of neonatal rats. Moreover, treatments with two GABA B receptor antagonists (CGP 35348 and CGP 55845) can remarkably improve the motor function and inflammatory response of 10-day-old rats subjected to the hypoxia-ischemia stimulation [137–139]. In another study [140], a GABA receptor agonist (topiramate) generated more damage to the brain and the cognitive ability injury in the hypoxic-ischemic brain of neonatal rats (over 7-day age), except for protective effect on hypoxic-ischemic brain injury in rats (1, 4-day age).…”