Interleukin (IL)-2 is a potent modulator of neurotransmission and neuronal development in the mesolimbic and mesostriatal systems. It is also implicated in pathologies (including schizophrenia, Parkinson's disease, autism, cognitive disorders) that are linked with abnormalities in these systems. Since the kainate receptor plays an essential role in mesolimbic neuronal development and excitability, we examined the effects of physiologically relevant concentrations of IL-2 on kainate-activated current (I(KA)) in voltage-clamped neurons freshly isolated from the ventral tegmental area (VTA) of 3- to 14-day-old rats. IL-2 (0.01-10 ng/ml) alone had no effect on membrane conductance. When co-applied with kainate, IL-2 significantly decreased I(KA). IL-2 (2 ng/ml) shifted the kainate concentration-response curve to the right in a parallel manner, significantly increasing the EC(50) without changing the maximal I(KA). IL-2 inhibition of I(KA) was voltage-dependent, being greater at negative potentials. IL-2 did not alter the reversal potential. These findings suggest that IL-2 potently modulates kainate receptors of developing mesolimbic neurons. We suggest that IL-2 plays a role in the excitability of developing neurons in the mesolimbic system. Inasmuch as increased I(KA) is associated with excitotoxicity, coupled with the present observation that IL-2 inhibits I(KA), we suggest an adaptive role for IL-2 in limiting excitotoxicity in the developing brain. IL-2 might thus be required for normal cell development in the mesolimbic and mesostriatal systems.