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The hypoglycemic effect of various amides of citric acid were evaluated by oral administration to alloxan-induced diabetic rats. The results indicated that monoesters of citric acid have higher hypoglycemic activity than the parent citric acid. The type of ester moiety and the length of the chain have an effect on the potency of hypoglycemic activity. The 2-ethyl and 2-methyl esters of citric acid, both of which have higher acidity, were the most potent in the series, and 2-ethyl citric acid was the most effective of the amides evaluated. Moreover, the oral hypoglycemic effect of 2-ethyl citric acid could be enhanced by the addition of paracetamol, an analgesic. These results suggest that 2-ethyl citric acid could be an important part of the compound in the therapeutic control of diabetes.Deficient conditioned fear extinction in bv/bv and in BW/BW rats.
Fear conditioning-extinction protocols are important paradigms to examine fear-related diseases such as anxiety disorders. Loss of signaling in the amygdala by the metabotropic glutamate receptor 5 (mGlu5) leads to impaired extinction of conditioned fear, associated with a disturbed signaling in the hippocampus. The mGlu5 receptor is encoded by GRM5, and GRM5 deficiency is associated with behavior and brain abnormalities in mice and rats. To examine if mGlu5 receptor deficiency is reflected in the regulation of conditioned fear extinction, we tested the performance of two rat strains, bv/bv and BW/BW, which are deficient in the mGlu5 receptor. Each rat strain was generated by mating a homozygous, GRM5-deficient male with a Wistar-Kyoto female (i. 0b46394aab