Indian Journal of Experimental Biology Vol. 46, March 2008, pp. 159-163 Gabapentin attenuates acute hypoxic stress–induced behavioral alterations and oxidative damage in mice: Possible involvement of GABAergic mechanism Anil Kumar & Richa Goyal Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160 014, India Received 16 April 2007; revised 21 January 2008 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. Keywords: Anxiety, Gabapentin, Hypoxic stress, Lipid peroxidation, Locomotor activity, Muscimol, Picrotoxin Hypoxia causes oxidative damage in different body organ systems including brain 1 . Hypoxic stress can cause cellular damage and neuro-degeneration by inducing the reactive oxygen species (ROS) that oxidize vital cellular components such as lipids, proteins and DNA 2 . Gamma–amino–butyric-acid (GABA) is one of the major inhibitory neurotransmitter for fast inhibitory synaptic transmission and regulates many physiological and psychological processes 3 . Role of GABAergic system in stress and related conditions has been well documented 4 . GABAergic system is influenced significantly during stress, particularly the GABA- benzodiazepine receptor binding sites 5 . The antiepileptic drug, gabapentin is a lipophilic analogue of the inhibitory neurotransmitter GABA and being highly lipid soluble, it readly crosses the blood brain barrier 6 . Gabapentin is reported to exhibit neuroprotective activity in posttraumatic stress disorders 7 . However, its exact mechanism of neuroprotective action is still unknown. The present study was designed to investigate the neuroprotective effect of gabapentin on acute hypoxic stress -induced behavioral alterations and oxidative damage in mice and to elucidate the mechanism involved in its neuroprotective action. Materials and Methods Albino mice (Laca strain) weighing between 22-30 g bred in Central Animal House (CAH) facility of the Panjab University, Chandigarh, India were used. The animals were housed under standard laboratory conditions and maintained on natural light and dark cycle and had free access to food and water. Animals were acclimatized to laboratory conditions before the experiment. Each group consisted of 6 animals. All experiments were carried out between 0900 and 1500hrs. The experimental protocols were approved by Institutional Animal Ethics Committee (IAEC) and conducted according to the Indian National Science Academy Guidelines for the use and care of experimental animals. Hypoxic stress in mice was induced for a period of 2 hr. Slow deprival of oxygen in the chamber resulted in increased respiratory rate, escape attempts and tremors 8 . Gabapentin (50 and 100 mg/kg, ip), picrotoxin (1.0 mg/kg) and muscimol (0.05 mg/kg) were dissolved in distilled water. To study their per se effects they were administered (1 ml/100g body weight) intraperitoneally 30 min before animals were subjected to hypoxic stress. For the interaction studies, picrotoxin or muscimol was administered 10 ____________ Phone : +91-172-2534106 Fax: +91-172-2541142 E-mail: kumaruips@yahoo.com