Effects of YM-14673, a new thyrotropin-releasing hormone analogue, on impaired learning of passive avoidance in mice.
The effects of YM-14673(N alpha-([(S)-4-oxo-2-azetidinyl] carbonyl)-L-histidyl-L-prolinamide dihydrate), a new thyrotropin-releasing hormone analogue, on impaired passive avoidance responses, were studied in mice in comparison with those of the thyrotropin-releasing hormone and its analogue DN-1417. In a test trial 24 hr after training, the latency in entering into a darkened compartment from an illuminated one was shortened by scopolamine and cycloheximide treatment. The shortened latency was prolonged in both models when YM-14673, thyrotropin-releasing hormone and DN-1417, in doses without effect on spontaneous movement and pain response by the hot plate method, were administered before training. This prolongation of shortened latency by the thyrotropin-releasing hormone and its analogues in cycloheximide-treated mice was antagonized by scopolamine but not by haloperidol. YM-14673 was about 10 times more potent than the thyrotropin-releasing hormone and DN-1417 in improving the impaired learning behavior. The shortened latency of step-through was ameliorated in scopolamine-treated mice when YM-14673 was administered immediately after training but not before testing. These results suggest that YM-14673, in addition to the thyrotropin-releasing hormone and DN-1417, facilitates the cerebral functioning, presumably by activating the cholinergic system.
Yamamoto
M
M
Institute of Applied Pharmacology and Development, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Ozawa
Y
Y
Takeuchi
H
H
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D001384:Azetidines / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology
D014150:Antipsychotic Agents; D001384:Azetidines; D004151:Dipeptides; D013973:Thyrotropin-Releasing Hormone; C054995:azetirelin; D003513:Cycloheximide; C029762:DN 1417; D012601:Scopolamine; D006220:Haloperidol