TIME-DEPENDENT MODULATION OF MORPHINE-INDUCED ANTINOCICEPTION BY CAPTOPRIL

Circadian changes in response to thermal stimulation were assessed by the hotplate test in groups of synchronized mice treated intraperitone ally with saline, captopril, morphine, and captopril plus morphine. Al l treatment groups exhibited significant rhythm profiles. Captopril it self did not possess statistically significant antinociceptive activit y when compared with the corresponding controls, but potentiated morph ine-induced analgesia particularly at the late phase of dark period. I t is concluded that the mechanism leading to this time-dependent poten tiation may be related either to the availability of captopril at the site of action or the diurnal fluctuations in the activity of brain en kephalinase.