In fact, the tricyclic antidepressant imipramine shortened immobility time in the forced swimming test, whereas 25 mg/kg 17-ODYA fluvoxamine maleate administered intraperitoneally or 2 mg/kg of cyclo administered orally had no effect on immobility time. Second, we conducted the water maze test using depressed mice previously subjected to repeated OS swimming, which induces a depression-like state in rats and mice. Antidepressants such as SSRIs were effective in this behavioral test. Actually, the escape latency in the water maze test of mice pretreated with OS swimming and repeatedly given fluvoxamine orally at a dose of 25 mg/kg decreased to the level of control mice. We conducted the radial maze test in rats and stepthrough passive avoidance test in scopolamine-impaired mice to investigate the anti-dementia effects of cyclo. Scopolamine interferes with A 286982 memory and cognitive function in humans and experimental animals by blocking muscarinic ACh receptors. Each arm in the radial maze test contains a food reward, and the rat is required to visit each arm once within a trial to locate all eight food rewards. Therefore, the task requires the animal to keep track of the already visited arms by making use of visuospatial cues located in the environment. A repeated visit to the same arm was counted as a working memory error during a test session. Our results show, for the first time, that the chicken essence beverage-derived DKP cyclo is a dual inhibitor of the SERT and AChE. Because DKPs seem almost ubiquitous in fermented or processed foods and beverages and are present in many organisms, we tested whether other DKPs could inhibit SERT and AChE. We found that cyclo, a compound endogenous to animals that shares the C-terminal dipeptide sequence with TRH, inhibited SERT but not AChE, and that cyclo, one of the bitter components of beer, inhibited AChE but not SERT. However, cyclo did not improve depression symptoms, possibly because of its much weaker affinity for SERT than that of cyclo. In contrast, oral administration of 200 mg/kg of cyclo significantly increased extracellular levels of ACh in the VHIPP. However, the same cyclo dose failed to improve the number of arms chosen within the first eight choices during the radial maze test, possibly because it had behavioral suppressing effects. The affinities of cyclo against SERT and AChE were fairly low compared with those of medical drugs such as the SERT inhibitors fluvoxamine and paroxetine and the AChE inhibitor donepezil. However, single oral administration at the dose of 200 mg/ml cyclo showed a tendency to increase 5-HT, NE, and DA in the mPFC, although the difference was not significant. However, extracellular ACh in the VHIPP increased significantly. Furthermore, significant increases in extracellular levels of 5-HT, NE, DA, and Ach were observed dose-dependently when once per day administration was continued for 14 consecutive days.