Daily variations of amino acid concentration in mediobasal hypothalamus, in rats injected with Freund's adjuvant. Effect of cyclosporine

Abstract

Although the existence of central responses to inflammatory injuries was already reported, the existence of hypothalamic amino acid responses has been less explored. The present study was designed to characterize the 24-h changes in mediobasal hypothalamic excitatory and inhibitory amino acid neurotransmitter contents and to analyze the effect of Freund's complete adjuvant administration on these patterns. Also the effects of the immunosuppressant drug Cyclosporine was studied. The content of aspartate, glutamate, glutamine, GABA and taurine was measured by HPLC with fluorimetric detection. The results show the existence of specific daily rhythms of aspartate, glutamate, glutamine, GABA and taurine contents in the mediobasal hypothalamus of control rats. Maxima for these amino acids was found at midnight, although another peak of lesser magnitude, occurred during the light phase of the photoperiod, except for TAU in which both peaks were of similar magnitude. Freund's complete adjuvant administration did not modify the 24-h pattern of any amino acid studied. It reduced the midnight peak of glutamate, glutamine and GABA and increased that of taurine. Moreover, it increased and extended the midday peak of glutamate. Besides, Freund's adjuvant did not modify aspartate content at any time point studied. Cyclosporine pretreatment did not prevent the inhibitory effects of Freund's complete adjuvant on glutamate, glutamine and GABA midnight peaks. However, the drug blocked the increase in the content of taurine at midnight and increased its midday peak. Moreover, cyclosporine administration abolished the variations of ASP during the scotophase, as compared to control animals and shift delayed both peaks of glutamate. The results indicate the existence of a significant effect of immune-mediated inflammatory response of the mediobasal hypothalamic amino acids studied, at an early phase after Freund's adjuvant administration, and that these changes were partially sensitive to the immunosuppression induced by cyclosporine.