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Title: Possible involvement of nitric oxide (NO) signaling pathway in the anti- depressant-like effect of MK-801(dizocilpine), a NMDA receptor antagonist in mouse forced swim test
Authors: Dhir, Ashish
Kulkarni, SK
Keywords: Cyclic guanosine monophosphate
Forced-swim test
Nitric oxide
MK-801 (dizocilpine)
Phosphodiesterase 5 inhibitor
Issue Date: Mar-2008
Publisher: CSIR
Abstract: L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) is an important signaling pathway involved in depression. With this information, the present study aimed to study the involvement of this signaling pathway in the antidepressant-like action of MK-801 (dizocilpine; N-methyl-d-aspartate receptor antagonist) in the mouse forced-swim test. Total immobility period was recorded in mouse forced swim test for 6 min. MK-801 (5-25 μg/kg., ip) produced a U-shaped curve in reducing the immobility period. The antidepressant-like effect of MK-801 (10 μg/kg, ip) was prevented by pretreatment with L-arginine (750 mg/kg, ip) [substrate for nitric oxide synthase (NOS)]. Pretreatment of mice with 7-nitroindazole (7-NI) (25 mg/kg, ip) [a specific neuronal nitric oxide synthase inhibitor] produced potentiation of the action of subeffective dose of MK-801 (5 μg/kg, ip). In addition, treatment of mice with methylene blue (10 mg/kg, ip) [direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase] potentiated the effect of MK-801 (5 μg/kg, ip) in the forced-swim test. Further, the reduction in the immobility period elicited by MK-801 (10 μg/kg, ip) was also inhibited by pretreatment with sildenafil (5 mg/kg, ip) [phosphodiesterase 5 inhibitor]. The various modulators used in the study and their combination did not produce any changes in locomotor activity per se and in combination with MK-801. MK-801 however, at higher doses (25 μg/kg, ip) produced hyperlocomotion. The results demonstrated the involvement of nitric oxide signaling pathway in the antidepressant-like effect of MK-801 in mouse forced-swim test.
Description: 164-170
ISSN: 0019-5189
Appears in Collections:IJEB Vol.46(03) [March 2008]

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