It is well known lipopolysaccharides (LPS) is produced by infected bacteria and triggers several acute phase responses after infection. Some reports show that rodents can acquire aversion to the taste stimulus paired with LPS^1-3). However, the brain mechanisms in the conditioned taste aversion (CTA) with LPS and in its retrieval remain obscure. In this study, we tried to visualize the brain activities by using the manganese enhanced MRI (MEMRI) ^4-5) due to elucidate the brain mechanism in the retrieval of CTA with LPS (LPS-CTA).Experiment 1: C57BL/6N male mice (10-12 weeks) were trained to drink distilled water (DW) for 10 min for 3 days. DW was deprived for 18 hs from day one of the training. Supplementation of water was for about 4 hs. On the conditioning day, mice were injected saline (Saline group), 0.3 M LiCl (127 mg/kg) (LiCl group), or 0.1 mg, 1 mg, or 10 mg/kg LPS after giving saccharin solution for 10 min in each group. All mice were tested to drink for 10 min on the Day 1-5 after the recovery for 3 days and measured body weight of the mice. Experiment 2: C57BL/6N male mice (10 weeks) were treated with the implantation of an intraoral cannula. The schedule for training to drink DW was the same as that of the experiment 1. All mice were given saccharin solution (0.4 ml) for 8 min through an intraoral cannula and were injected saline, LiCl, or LPS (1mg/kg) on the conditioning day. After recovery for 3 days, all mice were given saccharin solution and injected 20 mg/kg MnCl₂ to the stomach 30 min before MRI scanning. All mice were maintained in an anesthetized state by breathing 2.5% sevoflurane and fixed in the probe of the MR apparatus with a plastic holder. MEMRI was performed with an 11.7 T scanner (Bruker, BioSpec 117/11, AVANCE III, GmbH, Ettlingen, Germany). T1-weighted MR images were obtained every 30 min from 60 min before the stimulation (SE sequence, TE=11 ms, TR=400 ms, NEX=16). We compared the brain signal intensities especially at the brainstem, the central nucleus of the amygdala (CeA), and the dorsomedial hypothalamus (DMH), where are considered to be involved in CTA and in inflammation by LPS.Fig. 1 shows the saccharin intake on the conditioning day and Day 1-5 in each group. The saccharin intake of the LPS 1 mg, 10 mg, or LiCl groups decreased on the Day 1-3, in comparison with those on the conditioning day. The injection of the LPS 10 mg/kg induced weight loss after the conditioning. The mice in the LiCl and LPS (1mg/kg) groups expressed aversive behaviors, but not in the saline group. Fig. 2 shows the representative MR images and the average of the signal intensities at the CeA and the DMH of each group. The signal intensities of these regions in the LiCl and LPS groups were higher than that in the saline group. But there were no significant differences in the signal intensities of the brainstem among the groups. The signal intensity of the CeA in the LPS and LiCl groups were higher than that in the saline Group. The signal intensity of the DMH in the LPS group was higher than that in other groups.We investigated the effective dose of LPS on the acquisition of the conditioned taste aversion paradigm in the experiment 1. The result indicated that the high dose of LPS (10 mg/kg) provoked heavy inflammatory reaction. Therefore, we decided to use the 1 mg/kg of LPS in the experiment 2, where mice could acquire sufficient CTA without weight loss. We detected the significant signal changes at CeA and DMH in the retrieval of LPS-CTA by using MEMRI. The activities of the CeA, which is involved in the visceral input, are the same as the previous study using LiCl⁴⁾. LPS may evoke the visceral sensation as the same as LiCl. The signal intensity of DMH also increased by LPS-CTA. It is known that LPS induces body temperature changes accompanied by the inflammatory reaction. The hypothalamus including the DMH has a role of the body temperature control ⁶⁾. Therefore, there is a possibility that the activation of DMH in the retrieval of LPS-CTA might cause body temperature changes.We showed that LPS induces the conditioned taste aversion like LiCl. We applied MEMRI to detect the brain areas concerning in the retrieval of the CTA with LPS. We could detect the brain areas activated in the retrieval of LPS-CTA.