Lipopolysaccharide-mediated immobility in mice: reversal by cyclooxygenase enzyme inhibitors.
Endotoxin (lipopolysaccharide, LPS) is known to activate the hypothalamo-pituitary adrenocortical axis, as well as norepinephrine and indolamine metabolism. In the present study we examined the effects of systemically administered LPS on forced swimming-induced despair behavior in mice. LPS (50 micrograms/mouse i.p.) time-dependently enhanced the forced swimming-induced immobility period. The increase in immobility time was highest after 2 h of LPS administration. Desipramine (10 mg/kg), a tricycle antidepressant, or fluoxetine (10 mg/kg), a serotonin reuptake inhibitor, significantly reversed the LPS-induced increase in immobility time. Cyclooxygenase inhibitors nimesulide (1, 2 and 5 mg/kg), naproxen (10 mg/kg) and rofecoxib (2 mg/kg) did not alter the despair behavior per se. Nimesulide (10 mg/kg) did reverse reserpine-induced immobility. Nimesulide (2 mg/kg), naproxen (10 mg/kg) and rofecoxib (2 mg/kg) significantly reversed LPS-mediated despair behavior. The present study demonstrated that LPS-induced inflammatory responses in the brain may cause despair behavior. Reversal with a cyclooxygenase inhibitor indicates the role of prostaglandins in despair behavior.
Jain
N K
NK
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
Singh
A
A
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009288:Naproxen / Q000494:pharmacology; D012110:Reserpine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones; D013550:Swimming
D000929:Antidepressive Agents, Tricyclic; D016861:Cyclooxygenase Inhibitors; D003891:Desipramine; D004768:Enterotoxins; D005473:Fluoxetine; D007783:Lactones; D008070:Lipopolysaccharides; D009288:Naproxen; D012110:Reserpine; D017367:Selective Serotonin Reuptake Inhibitors; D013449:Sulfonamides; D013450:Sulfones; C082864:enterotoxin, Salmonella; C116926:rofecoxib; C012655:nimesulide