Interleukin-2 potentiates novelty- and GBR 12909-induced exploratory activity.
Interleukin (IL)-2 is a cytokine that influences exploratory behavior and central dopamine activity in rodents, and induces schizophrenic-like behavior and cognitive deficits in humans. We presently report that a single i.p. injection of murine IL-2 (0.05-0.80 microg/mouse) induced significant increases in novelty-induced locomotion and exploration in BALB/c mice. These measures were not significantly altered in mice that were pre-exposed to the test cage prior to cytokine injection. The IL-2-induced behavioral changes were not further augmented by repeated intermittent injections (five daily i.p. injections; 0.4 microg/mouse), however. Nonetheless, during the treatment period, activity scores of IL-2-treated mice significantly exceeded those of mice receiving saline; hence, repeated injections of IL-2 induced a persistent behavioral activation. IL-2 treatment also increased sensitivity to the behavior-stimulating effects of GBR 12909, a highly selective dopamine uptake inhibitor. This effect was a very long-lasting one since the dopamine agonist was administered 6 weeks after cessation of IL-2 treatment. The latter finding indicates that IL-2 interacts with the mesolimbic dopamine system, changing its sensitivity to seemingly different substances. Based on these data, and those of Zalcman and colleagues (S. Zalcman, I. Savina, R.A. Wise, Interleukin-6 increases sensitivity to the locomotor-stimulating effects of amphetamine in rats, Brain Res. 847 (1999) 276-283), it is suggested that cytokines can influence the development of behavioral abnormalities that are characteristic of aberrant mesolimbic dopamine activity via sensitization-like processes.
Zalcman
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Department of Psychiatry and Rutgers/UMDNJ Integrative Neuroscience Program, UMD-New Jersey Medical School, Medical Science Building, E-503, 185 S. Orange Ave., Newark, NJ 07103-2714, USA. zalcmass@umdnj.edu
D000818:Animals; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage
D018765:Dopamine Uptake Inhibitors; D007376:Interleukin-2; D010879:Piperazines; D011994:Recombinant Proteins; C043425:vanoxerine