MODULATION OF BEHAVIORAL AND NEUROCHEMICAL MEASURES OF FOREBRAIN DOPAMINE FUNCTION IN MICE BY SPECIES-SPECIFIC INTERLEUKIN-2

Interleukin-2 (IL-2) has recently been implicated as a modulator of br ain neuronal function and in the pathogenesis of several major neurops ychiatric disorders involving the dopamine system (e.g. schizophrenia and Parkinson's disease). Little is known, however, about the effects of IL-2 on dopamine-mediated behaviors. A series of behavioral experim ents were performed in mice to examine the hypothesis that species-spe cific IL-2 could modify behaviors known to be mediated by forebrain do pamine pathways. IL-2 administered subcutaneously produced a robust in crease in locomotor activity in an elevated plus-maze. No effects of t he cytokine were evident on measures of acoustic startle, prepulse inh ibition of the startle response (PPI), or fearfulness. In complementar y in vitro neurochemical experiments, to most closely assess physiolog ically relevant effects of the cytokine on dopamine release from stria tal neurons, species-specific IL-2 as well as high performance liquid chromatography (HPLC) were used to measure endogenous dopamine release from striatal slices. IL-2 dose-dependently modulated veratrine-evoke d release of endogenous dopamine in a biphasic pattern, increasing rel ease at lower concentrations and inhibiting release at a high concentr ation of the cytokine. In radioligand competition binding experiments, IL-2 was not active at striatal binding sites for [H-3]spiroperidol ( D-2-like receptors), [H-3]mazindol binding (dopamine uptake sites) and [H-3]SCH23390 (D-1-like receptors), indicating that the neuromodulato ry actions of IL-2 are not the result of direct or allosteric effects on dopamine receptors. Knowledge of the mechanisms by which IL-2 influ ences brain dopamine function could provide new insight into the patho physiology of forebrain dopamine neurons seen in disorders such as Par kinson's disease and schizophrenia.