Inhibitory influences of the adrenal steroid, 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone [correction of tetrahydroxycorticosterone] on aggression and defeat-induced analgesia in mice.

The effects of intraperitoneal administrations of the deoxycorticosterone metabolite, 5 alpha-pregnane-, 21 diol-20-one (3 alpha, 5 alpha-tetrahydrodeoxycorticosterone; alpha-THDOC) on the responses to aggression and defeat-induced analgesia were examined in subordinate intruder male mice in "resident-intruder" pairings. alpha-THDOC reduced in a dose-dependent mannter (1-20 mg/kg) the number of bites and time to obtain defeat in subordinate mice during the agonistic encounters, as well as attenuating defeat-induced analgesia. These inhibitory effects of alpha-THDOC were separate from its sedative actions at 20-30 mg/kg. In addition, the stereo-isomer, 3 beta-pregnane-3 alpha, 21 diol-20-one (20 mg/kg) had no significant effects on the agonistic encounters and defeat, indicating that the inhibitory effects of alpha-THDOC on agonistic interactions are stereospecific. Pretreatment with the benzodiazepine antagonist Ro 15-1788 (5 and 10 mg/kg) attenuated the inhibitory effects of alpha-THDOC on defeat-induced analgesia. Ro 15-1788 (5, 10 mg/kg) by itself, however, had minimal effects on these agonistic interactions and subsequent defeat-induced analgesia. These results indicate that the naturally occurring steroid, alpha-THDOC, has significant effects on responses to aggression and defeat-induced analgesia.