Interleukin-2-induced changes in behavioural, neurotransmitter, and immunological parameters in the olfactory bulbectomized rat.

The macrophage theory of depression proposes that abnormal secretions of the macrophage cytokines, an increase in interleukin (IL) 1, and a decrease in IL-2 may cause depression. The olfactory bulbectomized (OB) rat has been developed as an animal model of depression. In the present study, the effects of intracerebroventricular administration of IL-2 (10 U) for 7 days on behaviour, neurotransmitter concentrations, corticosterone levels, and some immune functions were investigated. In the novel environment of the 'open-field' apparatus, the OB rat showed increases in ambulation, rearing, grooming, and defaecation scores as compared with sham-operated animals. Following IL-2 administration, grooming and defaecation were significantly attenuated, while the ambulation and rearing scores were unaffected. In the elevated plus-maze, the increase in the time spent on the open arms of the maze by the OB animal was normalized by IL-2 administration. In the brain of untreated OB rats, the concentrations of noradrenaline were reduced; IL-2 treatment significantly increased the concentrations of noradrenaline and serotonin. After administration of IL-2 for 7 days, the impairments in the immune functions were also largely reversed in OB rats. Thus IL-2 significantly normalized the hyperactivity of mononuclear cells, the suppression of lymphocyte proliferation, and the reduction in the monocyte percentage in the white blood cell count in the OB rat. The concentrations of corticosterone in the serum of the OB rat were significantly reduced, but returned to control values following IL-2 treatment. The results suggest that IL-2 may have modulatory functions on behavioural, neurochemical, hormonal, and immunological aspects of the OB rat model of depression.