Inhibitory influences of the adrenal steroid, 3?, 5?-tetrahydroxycorticosterone on aggression and defeat-induced analgesia in mice

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Abstract
The effects of intraperitoneal administrations of the deoxycorticosterone metabolite, 5α-pregnane-, 21 diol-20-one (3α, 5α-tetrahydrodeoxycorticosterone; α-THDOC) on the responses to aggression and defeat-induced analgesia were examined in subordinate intruder male mice in “resident-intruder” pairings. α-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 α-THDOC were separate from its sedative actions at 20–30 mg/kg. In addition, the stereo-isomer, 3β-pregnane-3α, 21 diol-20-one (20 mg/kg) had no significant effects on the agonistic encounters and defeat, indicating that the inhibitory effects of α-THDOC on agonistic interactions are stereospecific. Pretreatment with the benzodiazepine antagonist Ro 15-1788 (5 and 10 mg/kg) attenuated the inhibitory effects of α-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, α-THDOC, has significant effects on responses to aggression and defeat-induced analagesia.