Short- and long-term effects of interleukin-2 treatment on the sensitivity of periadolescent female mice to interleukin-2 and dopamine uptake inhibitor.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Dopamine Uptake Inhibitors/*metabolism ; Dopamine Uptake Inhibitors/*pharmacology ; Interleukin-2/*metabolism ; Interleukin-2/*pharmacology; Animals ; Behavior, Animal/drug effects ; Brain/drug effects ; Brain/metabolism ; Dopamine/metabolism ; Dopamine Uptake Inhibitors/administration & dosage ; Female ; Interleukin-2/administration & dosage ; Male ; Mice ; Motor Activity/drug effects ; Time Factors

Interleukin (IL)-2, a T-helper 1 (Th1) cell-derived cytokine, which potently modulates dopamine activity and neuronal excitability in mesolimbic structures, is linked with pathological outcomes (e.g., schizophrenia, depression, etc.) that at least partly reflect alterations in central dopaminergic processes. It has been suggested that dopamine neurons undergo pruning during adolescence and abnormalities in pruning predispose individuals to behavioral disorders. Since IL-2 is known as a neurodevelopmental factor affecting associated behavioral processes, the present study tested whether IL-2 can modulate stereotypic behaviors in both the periadolescent and adult periods. This study determined whether IL-2 treatment would produce long-lasting changes in sensitivity to a later challenge with IL-2 or GBR 12909, a highly selective dopamine uptake inhibitor. Four experiments were conducted. Firstly, a decrease in novelty-induced stereotypic behavior was observed in BALB/c periadolescent mice (38 days of age) following IL-2 administration (0.4 µg/2 ml) relative to vehicle control. In the second experiment, an initial dose of IL-2 was given in the periadolescent period, but did not affect rearing responses. A second dose of IL-2 given to the animals 30 days later as adults, resulted in a significant increase in rearing behaviors relative to control animals. In the third experiment, separate groups of experimental and control mice were administered GBR 12909, a highly selective dopamine reuptake inhibitor, 30 days following treatment with either IL-2 or vehicle. It was noted that this experimental group, which initially received IL-2, exhibited stereotypy, as evidenced by increased sniffing behavior. A fourth experiment revealed that IL-2 administered in periadolesecence and adulthood had no effect on other motor responses, indicating that IL-2 selectively modulates selective stereotypic behaviors. The results provide evidence, for the first time, that long-term changes in stereotypy in periadolescent mice are linked to an IL-2 mechanism, possibly utilizing dopamine.

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0 (Dopamine Uptake Inhibitors)
0 (Interleukin-2)
VTD58H1Z2X (Dopamine)

Date Created: 20130530 Date Completed: 20131125 Latest Revision: 20211021

20221213

PMC3663806

10.1371/journal.pone.0064473

23717619