Interleukin-6 increases sensitivity to the locomotor-stimulating effects of amphetamine in rats

Interleukin (IL)-6 mediates brain-immune interactions, influences the survi val of postnatal mesencephalic and basal forebrain cells, influences mesoco rticolimbic dopamine and serotonin neurotransmission, and is linked with va rious central nervous system disorders. In the present study, single inject ions of IL-6 (1 or 2 mu g/Long-Evans rat, i.p.) induced modest elevations o f locomotor activity. The locomotor increases were not augmented by repeate d intermittent injections of IL-6 (five daily injections; 1 mu g/rat), howe ver. Nonetheless, repeated IL-6 treatment increased sensitivity to the loco motor-stimulating effects of 1.0 and 0.5 mg/kg amphetamine, when tested 5, 7, or 14 days following interruption of the cytokine treatment. The ability of acute IL-6 injections to alter locomotor activity and the ability of re peated IL-6 injections to produce long-lasting sensitization to the locomot or-stimulating effects of amphetamine suggest an interaction of this cytoki ne with the mesolimbic dopamine system, a system implicated in aspects of s chizophrenia, addiction, and movement disorders. The fact that IL-6 caused a lasting change in responsiveness to amphetamine implies a mechanism by wh ich immunogenic stimuli can alter brain circuitry, changing its sensitivity to seemingly unrelated subsequent stimuli or events. (C) 1999 Elsevier Sci ence B.V. All rights reserved.