THE EFFECT OF OLFACTORY BULBECTOMY IN THE RAT - ALONE OR IN COMBINATION WITH ANTIDEPRESSANTS AND ENDOGENOUS FACTORS, ON IMMUNE FUNCTION

The results from studies in the olfactory bulbectomized (OB) rat model of depression clearly show that the changes in the immune system following bulbectomy are similar to those reported in depressed patients. For example, mitogen-stimulated lymphocyte proliferation and neutrophil phagocytosis are reduced while monocyte activity is elevated. In the differential white cell (WBC) count, the percentage of neutrophils is increased and the lymphocytes is decreased. In addition, an increase in some of positive acute phase proteins and a decrease in negative acute phase protein albumin are also found in OB rats. The antidepressants, such as serotonin reuptake inhibitors (fluvoxamine and sertraline), the antihistamine terfenadine, the cytokine IL-2 and neuropeptide Y, which normalize both the brain noradrenergic and serotonergic system, attenuate the hyperactivity of OB rats in both the 'open field' and the open arms of the elevated plus-maze, and reverse the suppression in both lymphocyte proliferation and neutrophil phagocytosis. Antidepressants (desipramine and lithium) which have been shown to normalize the noradrenergic and/or dopaminergic system in OB rats, significantly reverse the hyperactivity of OB rats in the 'open field' and the reduced neutrophil phagocytosis. However, most of these antidepressants and endogenous factors fail to normalize the abnormalities in the WBC count. Thymopeptide treatment normalizes the WBC count, the changes in the noradrenergic and serotonergic systems and lymphocyte proliferation but fails to attenuate the hyperactivity in OB rats. The action of thymopeptides on the immune system is direct, while antidepressants and other agents may indirectly affect the immune systems, via neurotransmitters and cytokines. The results from these studies also demonstrate the causal relationship between endogenous factors (such as the thymopeptides, NPY, IL-2), the sigma ligand JO 1784 and depression.