Possible involvement of GABAergic modulation in the protective effect of gabapentin against immobilization stress-induced behavior alterations and oxidative damage in mice.
BACKGROUND
Acute stress may be experienced in response to an immediate physical, emotional or psychological stimulus. Stress has been known to affect several brain activities and promote long-term changes in multiple neural systems. In the present study, we investigated the possible involvement of GABAergic modulation in the protective effect of gabapentin in acute immobilization-induced behavioral alterations and oxidative damage in mice.


METHODS
Mice were immobilized for periods of 6 h. Animals were divided into different groups, consisting of six in each. Various GABAergic modulators were administered either alone or in their combinations, 30 min before subjecting the animals for immobilization stress. Various behavioral tests (mirror chamber, actophotometer) followed by oxidative parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were assessed in animals.


RESULTS
Six hours acute immobilization stress caused significant locomotor impairment, anxiety-like behavior in mice. Biochemical analyses also revealed an increase malondialdehyde, nitrite level and depletion of glutathione and catalase activity in 6 h stressed brains. Pretreatment with gabapentin (50 and 100 mg/kg, i.p.) significantly improved ambulatory movements, anti-anxiety effect (decreased time latency to enter in mirror chamber, increased number of entries and duration in mirror chamber) and antioxidative activity in stressed mice (P < 0.05). Further, picrotoxin (1.0 mg/kg) blocked and muscimol (0.05 mg/kg) potentiated the protective action of gabapentin (50 mg/kg). Results of both behavior as well as biochemical alterations in combination studies were significant as compared to their effect per se (P < 0.05).


CONCLUSIONS
Results of present study suggest GABAergic modulation might be involved in the protective effect of gabapentin against immobilization-induced behavior alteration and oxidative damage in mice.
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh - 160014, India. kumaruips@yahoo.com
Anil
A
Kumar
Richa
R
Goyal
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D000077206:Gabapentin; D005978:Glutathione / Q000378:metabolism; D007103:Immobilization; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D010084:Oxidation-Reduction; D010852:Picrotoxin / Q000494:pharmacology; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000588:Amines; D002374:Catalase; D003509:Cyclohexanecarboxylic Acids; D018757:GABA Modulators; D000077206:Gabapentin; D005978:Glutathione; D009118:Muscimol; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid