| The C75 (trans-3-carboxy-4-octyl-2-methylenebutyrolactones), a member of a-methylene-y-butyrolactones, is identified as the fatty acid synthase inhibitor and it is synthesized according to mechanisms of cerulenin. Recent studies show that central injection of C75 significantly causes anorexia and weight loss in rodents. And C75 exerts its actions through regulating neuropeptides in the hypothalamus, such neuropeptide Y. Many neuropeptides involved in learn and memory process. The present study was aimed to study the effect of C75 on learn and memory in mice. C75 was synthesized and purified by chemical method in our laboratory. C75 (1-10μg/mouse) was intracerebroventricular (i.c.v.) injected in mice. The short-term memory, long-term memory and spatial memory in mice were assessed by Y-maze test, step through passive avoidance task and Morris water maze test; and the locomotor acyivity was measured using the Autonomous Movement Instrument for Mice. The results demonstrated that C75 i.c.v. impaired short-term memory in Y-maze test and consolidation of memory in step-through passive avoidance task. However, C75 did not influence spatial memory in Morris water maze test and locomotor activity in mice.Apelin, the novel identified bioactive peptide first isolated from bovine stomach, has been demonstrated to the endogenous ligand for the APJ. Apelin is the derivant of preproapelin, a 77-amino-acid precursor, which is cleaved to several molecular fragments by enzymolysis in different sits in vivo, such as apelin-12, apelin-13, apelin-17 and apelin-36. Apelin and its receptor APJ widely distributes in both the central nervous system and the peripheral tissues and many biological effects have been found in the recent years, including regulation on cardiovascular system, inflammation, neuroendocrine, adipoinsular axis, food intake, drinking behavior and colonic motility. The present experiment was aimed to study the effect of central injection of apelin-13 on gastric emptying and intestinal transit in mice. I.c.v. administeration of apelin-13 (3 and 10μg/mouse) inhibited gastric emptying rate by 10.9% and 17.1%. This effect was significantly reversed by the APJ receptor antagonist apelin-13(F13A) and the opioid receptor antagonist naloxone, respectively. However, intraperitoneal (i.p.) injection of apelin-13 (10-100 μg/mouse) had no effect on gastric emptying rate. Apelin-13 (0.3,1,3μg/mouse, i.c.v.) decreased gastrointestinal transit rate by 16.8%,23.4% and 19.2%. This antitransit effect caused by apelin-13 could also be blocked by the apelin-13(F13A) and naloxone. In conclusion, all the data suggest that i.c.v. administered apelin-13 inhibits gastric emptying and intestinal transit in mice. It is supposed that this effect might be mediated via APJ receptor and opioid receptor in the brain in mice.
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