Beta amyloid peptide (Aβ1-40) can reduce long-term potentiation (LTP) and increase the levels of interleukin 1 beta (IL-1β) in the rat CA1 in vivo (Minogue et al., 2003). Here we have investigated the effects of IL-1 receptor antagonist (IL-1ra) on the Aβ-mediated depression of LTP. Extracellular field excitatory post synaptic potentials were recorded in the CA1 of urethane-anaesthetised rats. Aβ(1-40) (5ml,1nmol) and IL-1ra (5 ml, 350ng/ml) were injected icv. 1h prior to high frequency stimulation (HFS; 200Hz). Aβ caused a depression of LTP (130±7%, n=9) compared to controls (155±4%, n=17; P0.05) compared to controls and failed to reverse the Aβ-mediated depression of LTP when co-injected with Aβ (123±8%, n=9; P>0.05). There were increased levels of IL-1β in hippocampal tissue from animals injected with IL-1ra suggesting the possible presence of endotoxin due to the IL-1ra E. coli source. Consistent with this observation, injection of heat-treated IL-1ra caused a depression of LTP (117±12%, n=5; P<0.001). We therefore examined the effect of purified IL-1ra, which, when injected alone, caused a significant depression on LTP (137±7%, n=7; P<0.05) as compared to controls. Animals co-injected with Aβ and purified IL-1ra, however, showed an attenuation of the Aβ mediated depression of LTP (171±12%, n=5; P0.05). Our data draw attention to the source of experimental recombinant proteins, especially those prepared from E-coli. The half-life of IL-1ra is thought to be approximately 15min, which may explain the short-term effects of IL-1ra in attenuating the Aβ mediated depression of LTP. Biochemical analysis of the tissue derived from these experiments will help to shed light on the role of pro-inflammatory cytokines and the Aβ mediated depression on LTP. All procedures were performed under current local guidelines.