Interleukin-2 Treatment Induces an Acquired Behavioral Response Pattern (Repetitive Stereotyped Movements) Mediated by Dopamine D1 and D2 Receptors

Abstract

Interleukin (IL)-2 is implicated in the etiology of psychiatric disorders (e.g., schizophrenia, psychosis) involving an increased expression of repetitive stereotyped movements. However, little is known about the underlying pharmacological mechanisms or behavioral processes. Of further importance, we sought to identify underlying pharmacological mechanisms. We found that dopamine D1 receptors underlie the development of IL-2-induced stereotypic movements while D1 and D2 receptors are required for the expression of IL-2-induced stereotypies. These findings raised the intriguing possibility that IL-2 treatment induced an acquired behavioral response pattern requiring concurrent stimulation of D1 and D2 receptors. Thus, we determined whether stimulation of D1 and D2 receptors following termination of IL-2 treatment would re-instate the expression of repetitive stereotyped movements (i.e., an acquired response pattern). Based on these findings, we suggest that sub-chronic or chronic elevations in peripheral IL-2 levels may produce behavioral disturbances that persist beyond the presence of IL-2 by altering dopamine receptor activity resulting in the acquisition of an abnormal response pattern, and thus increase vulnerability to psychopathological outcomes associated with repetitive stereotyped movements. To our knowledge, these are the first data to identify a process by which a cytokine produces an abnormal response pattern.