Despite a vast amount of research into the actions of cytokines within the central nervous system, the pharmacological role and/or physiological function of the various cytokines within the central nervous system is still not fully understood. The present study evaluated the effects of intracerebroventricular administration of interleukin-1β, -2, -6 (20 ng) and tumour necrosis factor-α (40 ng) on elevated plus maze behaviour, monoamine levels in the hypothalamus, hippocampus and amygdala, plasma corticosterone and catecholamine concentrations and Concanavalin A-induced splenic lymphocyte proliferation in the rat. Both interleukin-1β and tumour necrosis factor-α induced 'anxiogenic-like' effects on the elevated plus maze, whereas interleukin-2 and interleukin-6 did not. However only interleukin- 1β led to endocrine variations often associated with stress and anxiety. Cytokine specific alterations in monoamine levels were evident in the hypothalamus and hippocampus, while neurotransmitter concentrations in the amygdala were not significantly altered by cytokine treatment. In addition, interleukin-1β reduced Concanavalin A-induced lymphocyte proliferation, whereas the other cytokine treatments failed to significantly alter this response. These results demonstrate that in some, but not all, respects interleukin-1β administration produced 'stress like' effects on behaviour, monoamine neurotransmitters, hypothalamic-pituitary-adrenal axis activity and immune function, while the other cytokines produced less consistent effects on these parameters. It is noteworthy that although interleukin-1β and tumour necrosis factor-α provoked an anxiogenic response in the elevated plus maze test of anxiety, neither cytokine significantly altered amygdaloid noradrenergic or serotonergic activity, as many previous studies have implicated increased amygdaloid noradrenergic and/or serotonergic activity in the pathophysiology of anxiety.

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Keywords Anxiety, Cytokine, HPA-axis, Monoamines, Psychoneuroimmunology, Stress
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Journal Neuroscience
Connor, T.J., Song, C., Leonard, B.E., Merali, Z., & Anisman, H. (1998). An assessment of the effects of central interleukin-1β, -2, -6, and tumor necrosis factor-α administration on some behavioural, neurochemical, endocrine and immune parameters in the rat. Neuroscience, 84(3), 923–933. doi:10.1016/S0306-4522(97)00533-2