Gabapentin attenuates acute hypoxic stress-induced behavioral alterations and oxidative damage in mice: possible involvement of GABAergic mechanism.
The effect of gabapentin has been investigated on acute hypoxic stress-induced behavioral alterations and oxidative damage in mice. Mice were subjected to hypoxia for 2 hr. Treatment with gabapentin (50 and 100 mg/kg) significantly increased ambulatory movements, exerted anti-anxiety like effect and reduced oxidative damage in mice subjected to acute hypoxic stress. Treatment with picrotoxin (1.0 mg/kg) per se had no significant effect on behavioral and biochemical parameters of stressed mice. Treatment with muscimol (0.05 mg/kg) per se significantly increased the locomotor activity of stressed mice, exerted significant anti anxiety effect and significantly reduced the oxidative damage. Further, pretreatment with picrotoxin (1.0 mg/kg) significantly blocked whereas pretreatment with muscimol (0.05 mg/kg) significantly potentiated the neuroprotective effect of gabapentin. These results suggest that gabapentin produces its neuroprotective effect in mice subjected to acute hypoxic stress through GABA(A) receptor mechanism.
Kumar
Anil
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. kumaruips@yahoo.com
Goyal
Richa
R
D000588:Amines / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000077206:Gabapentin; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology / Q000627:therapeutic use; D013053:Spectrophotometry; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000627:therapeutic use*
D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D009118:Muscimol; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid