THE EFFECTS OF CORTICOSTERONE ON 5-HT RECEPTOR FUNCTION IN RODENTS

In the mouse, administration of corticosterone-21 -acetate (30 mg/kg, s.c. daily) for 3 and 10 days produced an attenuation of the hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2 (di-n-propylamino)tetralin (8-OH-DPAT), which was not present after administration for 1 day. A similar effect was observed in the rat after administration of corticosterone-21-acetate (30 mg/kg, s.c. daily) for 10 days. Mice which had been given corticosterone for 10 days displayed the serotonin syndrome when injected with 5-hydroxytryptophan (5-HTP, 100 mg/kg, s.c.), 15 min after injection of carbidopa (25 mg/kg, i.p.). This was not seen in control animals. The serotonin syndrome was also induced in mice using 8-OH-DPAT; this increased in a dose-dependent manner and could be significantly decreased by pre-treatment with 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)-piperazine (NAN-190 5mg/kg, i.p., 30 min prior to administration of 8-OH-DPAT), a 5-HT1A receptor antagonist. Administration of corticosterone (30 mg/kg, s.c. daily) did not significantly alter the serotonin syndrome induced in treated mice, compared with controls. Mice pre-treated for 3 or 10 days with corticosterone did not differ from controls in the number of head-twitches induced by 5-HTP and carbidopa or 5-methoxy-N,N-dimethyltryptamine, nor did they differ from controls in their response to the putative 5-HT1B agonist 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) 1-H indole (RU 24969, 3 mg/kg, i.p.). In the rat, similarly, administration of corticosterone-21-acetate (30mg/kg, s.c. daily) for 3 and 10 days did not produce significant changes in the motor behavioural responses to 8-OH-DPAT.