Interleukin-2-induced increases in climbing behavior: inhibition by dopamine D-1 and D-2 receptor antagonists

Interleukin (IL)-2 is a potent modulator of dopamine activity in the mesocorticolimbic and mesostriatal systems. It is also associated with behavioral changes (increased motor activity) and psychopathological outcomes (schizophrenia, Parkinson's Disease, cognitive deficits) that at least partly reflect aberrations in central dopaminergic transmission. Nonetheless, there is no evidence that a functional link exists between IL-2, dopaminergic processes, and related behavioral changes. We thus determined if IL-2 treatment increases the expression of climbing behavior, a behavior that is linked with dopamine D-1 and/or D-2 receptors and one used to test the efficacy of neuroleptics. IL-2 treatment (5-daily i.p. injections; 0.4 microg/BALB/c mouse) induced a marked 2-fold increase in climbing scores; a single injection had no effect. IL-2-induced increases in climbing behavior were completely blocked by a selective dopamine D-1 receptor antagonist (SCH 23390; 0.05 or 0.2 mg/kg; i.p.), or by a relatively high dose of a D-2 antagonist (sulpiride; 80 mg/kg; i.p.). In contrast, MK-801, a noncompetitive NMDA receptor antagonist, had no effect. This is the first demonstration of a functional link between IL-2, dopaminergic receptors, and behavior. These findings could shed light on the mechanisms by which IL-2 increases vulnerability to psychiatric abnormalities associated with aberrations in central dopaminergic processes.