Possible GABAergic Modulation in the Protective Effect of Zolpidem in Acute Hypoxic Stress-induced Behavior Alterations and Oxidative Damage |
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Authors: | Anil Kumar Richa Goyal |
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Institution: | (1) Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India |
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Abstract: | Hypoxia is an environmental stressor that is known to elicit alterations in both the autonomic nervous system and endocrine
functions. The free radical or oxidative stress theory holds that oxidative reactions are mainly underlying neurodegenerative
disorders. In fact among complex metabolic reactions occurring during hypoxia, many could be related to the formation of oxygen
derived free radicals, causing a wide spectrum of cell damage. In present study, we investigated possible involvement of GABAergic
mechanism in the protective effect of zolpidem against acute hypoxia-induced behavioral modification and biochemical alterations
in mice. Mice were subjected to acute hypoxic stress for a period of 2 h. Acute hypoxic stress for 2 h caused significant
impairment in locomotor activity, anxiety-like behavior, and antinocioceptive effect in mice. Biochemical analysis revealed
a significant increased malondialdehyde, nitrite concentrations and depleted reduced glutathione and catalase levels. Pretreatment
with zolpidem (5 and 10 mg/kg, i.p.) significantly improved locomotor activity, anti-anxiety effect, reduced tail flick latency
and attenuated oxidative damage (reduced malondialdehyde, nitrite concentration, and restoration of reduced glutathione and
catalase levels) as compared to stressed control (hypoxia) (P < 0.05). Besides, protective effect of zolpidem (5 mg/kg) was blocked significantly by picrotoxin (1.0 mg/kg) or flumazenil
(2 mg/kg) and potentiated by muscimol (0.05 mg/kg) in hypoxic animals (P < 0.05). These effects were significant as compared to zolpidem (5 mg/kg) per se (P < 0.05). Present study suggest that the possible involvement of GABAergic modulation in the protective effect of zolpidem
against hypoxic stress. |
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Keywords: | Anxiety Analgesia Flumazenil Hypoxic stress Locomotor activity Zolpidem |
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