Olfactory bulbectomy provokes a suppression of interleukin-1 beta and tumour necrosis factor-alpha production in response to an in vivo challenge with lipopolysaccharide: Effect of chronic desipramine treatment

The olfactory bulbectomized (OB) rat has been developed as an animal model of depression and exhibits several behavioural and neurochemical characteri stics that are qualitatively similar to those found in clinically depressed patients. In addition to the behavioural and neurochemical abnormalities s een in OB rats, it has been reported that these animals have alterations in a number ex vivo measures of immune function many of which are reversed fo llowing chronic antidepressant treatment. In the present study we sought to examine the effects of olfactory bulbectomy on responsiveness to an in viv o immune challenge with bacterial lipopolysaccharide (LPS; 100 mu g/kg, i.p .). In addition, the effect of chronic treatment with the tricyclic antidep ressant desipramine (7.5 mg/kg, i.p.) on bulbectomy related behavioural cha nges, hypothalamic-pituitary-adrenal axis activity and immune responsivenes s was evaluated. To our knowledge this is the first time that in vivo immun ological responsiveness has been examined in the OB rat model of depression . OB rats exhibited a characteristic hyperactive response in a novel 'open field' environment, which was attenuated following chronic desipramine trea tment. LPS provoked a large increase in circulating interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha in vehicle treated sham operated an imals. Vehicle treated OB rats displayed a significant impairment in LPS-in duced IL-1 beta (54%) and TNF-alpha (70%) secretion compared to their sham operated controls, an effect that was potentiated following chronic desipra mine treatment. Furthermore, sham animals that were chronically treated wit h desipramine displayed decreases in LPS-provoked IL-1 beta (51%) and TNF-a lpha (49%) secretion compared to vehicle treated counterparts. In addition, LPS-induced alterations in corticosterone and adrenal ascorbic acid concen trations were also attenuated by bulbectomy, an effect that was further enh anced following chronic desipramine treatment. In conclusion, these data pr ovide evidence that olfactory bulbectomy in the rat impairs the ability of macrophages to produce the proinflammatory cytokines IL-1 beta and TNF-alph a following an in vivo challenge with bacterial LPS. Whilst chronic treatme nt with desipramine normalized the behavioural hyperactivity observed in OB rats, such treatment further impaired LPS-induced IL-1 beta and TNF-alpha secretion in bulbectomized rats. Copyright (C) 1999 S. Karger AG, Basel.