EFFECTS OF GLUCOCORTICOIDS ON 5-HT1A PRESYNAPTIC FUNCTION IN THE MOUSE

8-OH-DPAT, a selective 5-HT1A agonist, produced a hypothermic response in mice at a dosage of 0.5 mg/kg. Administration of corticosterone-21 -acetate (0.5, 5 and 50 mg/kg, daily for 3 and 10 days) produced a dos e-dependent attenuation of this hypothermic response in mice. When all controls and corticosterone treated mice were retested, 14 days after initial testing, they did not differ in the hypothermic responses ind uced by 8-OH-DPAT. Mice treated with aldosterone (50 mg/ kg), dexameth asone (50 mg/kg) and the specific type 2 corticosteroid receptor agoni st, ydroxy-21-methyl-17a-pregna-1,4,6-trien-20-yn-3-on (RU26988, 30 mg /kg) for 10 days, did not differ from vehicle treated controls in the hypothermic response to 8-OH-DPAT. Mice administered corticosterone-21 -acetate (30 mg/kg, daily) for 10 days displayed a motor behavioural s yndrome, which was not seen in controls, when injected with 5-hydroxyt ryptophan (5-HTP, 100 mg/kg) 15 min after the injection of carbidopa ( 25 mg/kg). This was significantly decreased by pretreatment with the 5 -HT1A receptor antagonist 2-methoxyphenyl)-4-(4-phthalimidobutyl)-pipe razine (NAN-190 5 mg/kg, 30 min prior to administration of carbidopa). Taken together, this evidence is compatible with a specific corticost erone induced facilitation of 5-HT release due to attenuation of inhib itory 5-HT1A autoreceptor function.