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Possible involvement of GABAergic modulation in the protective effect of gabapentin against immobilization stress‐induced behavior alterations and oxidative damage in mice
Author(s) -
Kumar Anil,
Goyal Richa
Publication year - 2007
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2007.00524.x
Subject(s) - malondialdehyde , gabapentin , oxidative stress , glutathione , pharmacology , chemistry , gabaergic , anxiolytic , nitrite , catalase , picrotoxin , endocrinology , medicine , biochemistry , gabaa receptor , receptor , nitrate , pathology , alternative medicine , organic chemistry , enzyme
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. Materials and 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). Conclusion 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.