A rearing episode was defined as a subject lifting both front limbs off the ground, whereas a rearing episode against the wall consisted of lifting both front limbs and leaning against the cage wall. We selected these stereotypic measures based on our findings that IL-2 treatment induces an increase in stereotypic motor behavior, showing that those behaviors may be attributed to elements of an activated immune system and their utility as animal analogous of repetitive stereotypic movements. In the present study, we showed for the first time that cytokine administration induces significant and long-lasting behavioral variations in periadolescent mice. Specifically, a single injection of IL-2 induced significant decreases in novelty-induced stereotypic behavior, possibly indicating a ����depressive-like���� state, which did not significantly change overall activity in the horizontal or vertical directions. This finding therefore reveals an absence of non-specific motor effects of IL-2 upon stereotypic behaviors tested in this study. Of further importance, adult responses to IL-2 or psychostimulant challenge were significantly enhanced in mice with a history of IL-2 treatment during periadolescence. Thus, a single injection of IL-2 during the periadolescent period has important consequences on adult responses. This suggests a temporal specificity upon selective behavioral motor responses that are associated with specific ages of the animals examined in this study. In addition, based upon the recent findings of Zalcman et al., it is also likely that these effects are mediated through specific anatomical loci and their associated pathways. Of central importance is the question of whether IL-2 can influence behavioral processes via their influence on brain function. The neurochemical and behavioral effects of peripherally Methoxy-X04 applied IL-2 are related to its ability to cross the blood-brainbarrier, but its mode of entry is unclear. In adults, the molecular weights of cytokines are sufficiently large to prevent them from crossing the BBB alone to activate neurons by specific receptor mechanisms or to produce corticotropin-releasing hormone. In adolescents, the blood brain barrier may be more porous and underdeveloped and therefore, pro-inflammatory cytokines may enter through the ����leakier���� area, act on brain regions lacking one of these barriers or they may enter the brain via ����specific uptake systems����. Under conditions when IL-2 is able to cross the BBB, it has been shown to influence dopamine turnover in the prefrontal cortex and dopamine release in the nucleus accumbens. There is also evidence for entrance of T1-Lymphocytes MDL 100907 directly into the CNS across the BBB in experimental allergic encephalomyelitis and other experimental models, which may be affected by inflammatory states.