Protective effect of cyclooxygenase‐2 (COX‐2) inhibitors but not non‐selective cyclooxygenase (COX)‐inhibitors on ethanol withdrawal‐induced behavioural changes

Abstract

Cyclooxygenase (COX) is reported to play a significant role in neurodegeneration. Recent studies have shown that chronic ethanol administration up-regulates cyclooxygenase expression. In the present study we examined the effect of nimesulide (a preferential COX-2 inhibitor), rofecoxib (a highly selective COX-2 inhibitor) or naproxen (a non-selective COX-inhibitor displaying high affinity towards the COX-1 isoenzyme) on alcohol-induced withdrawal symptoms. Mice were made physically dependent on alcohol by the chronic administration of ethanol (2 g/kg of 10% v/v), intragastrically, twice on day 1 and then once-daily on successive days for a total of 7 days. Nimesulide [2.5 mg/kg, intraperitoneally (i.p.)], rofecoxib (2 mg/kg, i.p.) or naproxen (7 mg/kg, i.p.) were administered daily for 7 days before administering alcohol intragastrically. After 24 hours of the last alcohol administration, the treatments were reversed and the mice were tested for withdrawal, so that the animals that had received COX-inhibitors followed 30 minutes later by ethanol on days 1-7 were challenged with saline. Similarly, the animals which received saline followed 30 minutes later by ethanol received only saline. Behavioural analysis revealed hyperlocomotor activity, increased anxious response and increased hyperalgesia in mice. Also, alcohol withdrawal decreased the threshold for Pentylenetetrazole-(PTZ)-induced convulsions. Pretreatment with COX-inhibitors rofecoxib (2 mg/kg, i.p.) or nimesulide (2.5 mg/kg, i.p.) displayed significant protection against ethanol-induced withdrawal symptoms, while naproxen (7 mg/kg, i.p.) was not effective in reversing alcohol-induced withdrawal symptoms. The results of the present study suggest strongly the possible role of cyclooxygenases, particularly COX-2 inhibitors, on ethanol-induced withdrawal symptoms and the potential use of COX-2 inhibitors in their prevention and treatment.

Antidepressant activity of curcumin: involvement of serotonin and dopamine system

“…Reserpine was dissolved with the help of a few drops of acetic acid and the volume was made up with distilled water, whereas curcumin and piperine were dissolved in rice bran oil. The doses of the drugs used were selected according to the previous studies conducted in our laboratory (Dhir et al 2005;Kulkarni and Mehta 1985) and as reported in the literature (Xu et al 2005a, b). All the drugs were administered intraperitoneally in a fixed volume of 1 ml/100 g body weight.…”

“…Briefly, mice were allowed to acclimatize to the observation chamber for a period of 2 min. Locomotion was expressed in terms of total number of ambulations (total photobeams counts) during a 5-min test for each mouse (for details, see Dhir et al 2005).…”

Nimesulide, a cyclooxygenase-2 (COX-2) inhibitor counteracts immobilization stress-induced alterations in different behavioral and biochemical parameters in mice

“…The stress was given 6 hrs daily for 7 days. The dose of nimesulide (2.5 mg/kg) used was previously standardized in our laboratory (Dhir et al, 2005).…”

Effect of Addition of Yohimbine (Alpha-2-Receptor Antagonist) to the Antidepressant Activity of Fluoxetine or Venlafaxine in the Mouse Forced Swim Test

“…Mice were allowed to acclimatize to the observation chamber for a period of 2 min. Locomotion was expressed in terms of total photobeam counts per 5 min per animal [12] .…”