Effects of the LHRH antagonist Cetrorelix on the brain function in mice.
The decapeptide Cetrorelix, an LHRH antagonist, inhibits gonadotropin and sex steroid secretion. Cetrorelix is used for IVF-ET procedures and for the treatment of patients with prostate carcinoma, benign prostatic hyperplasia, endometriosis, leiomyomas and, ovarian cancer. However little is known about the effects of Cetrorelix on the brain function. In the present work the influence of Cetrorelix on different aspects of the brain function was studied following its administration into the lateral brain ventricle in mice. The effects tested included the impairment of the consolidation of a passive avoidance reflex caused by beta-amyloid 25-35, anxiolytic action in the plus-maze, antidepressive action in a forced swimming test and a tail suspension test and open-field behavior. In the passive avoidance test, beta-amyloid 25-35 administered immediately after the learning trial impaired the consolidation of passive avoidance learning. Cetrorelix fully blocked the impairment of the consolidation of passive avoidance learning when given icv 30 min following beta-amyloid 25-35 administration. If beta-amyloid 25-35 and Cetrorelix icv were given simultaneously, the Cetrorelix attenuated, but did not block the action of the beta-amyloid 25-35. Cetrorelix elicited anxiolytic action in the plus-maze, depending on the dose used. In the forced swimming and tail suspension tests, Cetrorelix demonstrated antidepressive-like action. Concerning open-field behavior, Cetrorelix displayed no action on locomotion, rearing or grooming. The results demonstrate that Cetrorelix affects brain function: and is able to correct the impairment of the memory consolidation caused by beta-amyloid 25-35. Cetrorelix also elicits anxiolytic and antidepressive action, but it does not influence the open-field activity. Further experimental work with Cetrorelix is necessary, but the results imply the possible merit of a clinical trial with Cetrorelix in patients with anxiety, depression and Alzheimer's disease.
Department of Pathophysiology, University of Szeged, Semmelweis 1, 6701 Szeged, Csongrad, Hungary. telegdy@patph.szote.u-szeged.hu
Gyula
G
Telegdy
Masaru
M
Tanaka
Andrew V
AV
Schally
D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003863:Depression / Q000188:drug therapy; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D020547:Lateral Ventricles; D051379:Mice; D009043:Motor Activity / Q000187:drug effects
D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix