REDUCTION OF CEREBELLAR GABA(A) RESPONSES BY INTERLEUKIN-1 (IL-1) THROUGH AN INDOMETHACIN INSENSITIVE MECHANISM

Recently, a role of IL-1 in the central nervous system has been descri bed, principally a fever-inducing effect in the hypothalamus through a prostaglandin second messenger system. IL-1 has also been shown to po tentiate gamma-aminobutyric acid (GABA(A)) responses in embryonic chic k neurones. This study describes the investigation of the effect of IL -1 on GABA(A) responses within the in vitro rat cerebellar slice, a pr eparation containing intact neuronal circuitary. Stimulation of the ar ea of passage of parallel fibres produced a pure GABA(A) inhibition of the spontaneous firing of Purkinje cells. 5 and 10 ng/ml IL-1 produce d a reduction in the duration of inhibition 10 min after beginning per fusion of IL-1. This effect reversed within 15 min of washing out the IL-1. 10 ng/ml IL-I also reduced the effects of exogenously-applied GA BA (0.1 mM) with the same time course. In the presence of 1 mu M indom ethacin, there was no change in the effect of the IL-1. It can therefo re be concluded that the reduction in cerebellar GABAA responses by IL -1 is not mediated by the indomethacin-sensitive prostaglandin second messenger system.