The decapeptide
LHRH antagonist,
Cetrorelix, inhibits
gonadotropin and sex-
steroid secretion.
Cetrorelix is used for IVF-ET procedures and for the treatment of
benign prostatic hyperplasia,
endometriosis and
leiomyomas. However little is known about the effects of
Cetrorelix on brain functions. Previously we have tested
Cetrorelix in mice on the impairment of the consolidation of a passive avoidance behavior caused by
beta-amyloid 25-35,
anxiolytic action in the plus-maze, antidepressive action in a forced swimming test, tail suspension and open-field behavior following its administration into the lateral brain ventricle. In the present study we repeated and extended the experiments in rats in order to determine whether there are species differences in the action of
Cetrorelix between mice and rats. The effects of
Cetrorelix evaluated included the methods used in mice without tail suspension test and extended by measuring core temperature.
Cetrorelix fully blocked the impairment of the consolidation of passive avoidance learning when given icv 30 min following administration of
beta-amyloid 25-35. If
beta-amyloid 25-35 and
Cetrorelix were given simultaneously,
Cetrorelix was ineffective.
Cetrorelix elicited slight anxiogenic and stronger
anxiolytic action in the plus-maze, depending on the dose used. In the forced swimming tests,
Cetrorelix showed antidepressive-like action. In open-field behavior tests
Cetrorelix displayed a U-type action on locomotion with 0.5 and 2 microg increasing locomotion, and increase rearing but and had no effect on grooming at 0.5-2 microg.
Cetrorelix had no action on core temperature. Our findings demonstrate that
Cetrorelix is able to correct the impairment of the memory consolidation caused by
beta-amyloid 25-35.
Cetrorelix elicits
anxiolytic and antidepressive action, slightly increases locomotion and rearing in open field, but it does not influence the core temperature. The results obtained in rats are similar to those reported previously by us in mice. Collectively our findings confirm the effects of
Cetrorelix on brain function in two species and suggest the possible merit of a clinical trial with
Cetrorelix in patients with anxiety, depression and
Alzheimer's disease.