BEHAVIORAL-EFFECTS OF INTERLEUKIN-1-BETA - MODULATION BY GENDER, ESTRUS CYCLE, AND PROGESTERONE

Endogenous release or exogenous administration of the cytokine Interle ukin-1 (IL-1) produces several behavioral alterations, including suppr ession of locomotion and exploration. Because there are bidirectional interactions between IL-1 and the hypothalamic-pituitary-gonadal axis, we investigated possible differences between males and females in var ious phases of the estrus cycle in the behavioral effects of IL-1. In addition, we assessed the role of progesterone in mediating estrus cyc le-dependent differences in these effects. Female rats in either the e strus or the non-estrus phase of their cycle and male mts were injecte d with either IL-1 beta (2 or 5 mu g/kg) or saline. Activity in the op en field test was measured 2 h later by counting the number of line cr ossings and rearings. In saline-injected rats, nonestrus females perfo rmed less line crossings than estrus females. IL-1 produced a signific ant dose-dependent reduction of line crossing in males and estrus fema les. In contrast, in nonestrus females the lower dose of IL-1 had no e ffect, and the effect of the higher dose was significantly smaller in nonestrus than in estrus females. The higher dose of IL-1 suppressed r earing in all three groups, but the effect of the lower dose on the nu mber of rearings was significant only in estrus females. In a second e xperiment, ovariectomized females were injected with either progestero ne (2 mg/rat) or oil, followed 2 h later by an injection of either IL- 1 beta (2 mu g/kg) or saline. Activity was measured continuously by a biotelemetric system. IL-1 reduced activity in progesterone-treated ov ariectomized females but not in oil-injected controls. These findings suggest that changes in progesterone secretion along the estrus cycle modulate the behavioral responsiveness to IL-1 in female rats. (C) 199 5 Academic Press, Inc.