An LH-RH antagonist inhibits the behavioral effects of the agonist D-TRP-6-LH-RH in mice.

The effects of a potent LH-RH receptor antagonist, [Ac-4-Cl-D-Phe1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH (ORG 30276), on the behavioral actions of the LH-RH agonist, D-Trp-6-LH-RH, were studied in mice. The subcutaneous (SC) administration of 100 micrograms/kg D-Trp-6-LH-RH inhibited ambulation in an open-field, produced analgesia in the hot-plate and tail-flick tests. These effects of the agonist were totally antagonized by pretreatment with ORG 30276 at a dose of 100 micrograms/kg SC. In the apomorphine-induced cage-climbing test, both the agonist and the antagonist alone or together suppressed the duration of stereotyped behavior in dose-dependent manner, but, as there was no additive synergism after combined treatments, it seems that the two substances mutually diminish each other's effects. The results indicate that the behavioral effects of the LH-RH agonist can be antagonized by pretreatments with a potent LH-RH antagonist designed to block pituitary LH-RH receptors, with the exception of the suppression of apomorphine-induced cage-climbing, where special type of receptors and/or mechanisms might be involved.