Effect of non-steroidal anti-inflammatory drugs on behavioral actions of diazepam in mice

ABSTRACT

To investigate the behavioral pharmacological interactions of diazepam with non steroidal anti-inflammatory drugs. Non selective cyclooxygenase enzyme inhibitors [100 mg/kg acetylsalicylic acid, 10 mg/kg indomethacin, and 10 mg/kg diclofenac], a selective cyclooxygnase-1 inhibitor [10mg/kg acetylsalicylic acid], and a selective cyclooxygnase-2 inhibitor [10 mg/km celecoxib] of non steroidal anti-inflammatory drugs were individually pretreated to 15 and 24 groups of Albino mice for dose and time dependent models [n=8, each treatment] before sleeping induced by diazepam [20 mg/kg, intraperitoneally]. In 6 groups using an open field and 4 groups using traction test models [n=10], 5 and 10 mg/kg of diazepam, intraperitoneally were given to induce sedation and muscle relaxation, and 2mg / kg, to induce anxiolytic action after treatment with acetylsalicylic acid [10 mg/kg] to 4 groups [n=6]. This study was carried out at the Al-Fateh Medical Science University, Tripoli, Libya between February and May 2009. In dose and time dependent models non selective cyclooxygenase and selective cyclo-oxygnase-1 inhibitors significantly reduced the duration of sleep induced by diazepam in mice by 60-75%, while the selective cyclooxygnase-2 inhibitor did not [p>0.05]. However, anxiolytic, muscle relaxant, and sedative effects of diazepam were unchanged by acetylsalicylic acid. Non-steroidal anti-inflammatory drugs, most likely cyclooxygenase selective-1 inhibitors reduced the duration of sleep induced by diazepam, and this interaction could be of a pharmacodynamic type