The neurosteroid, 3alpha-androstanediol, prevents inhibitory avoidance deficits and pyknotic cells in the granule layer of the dentate gyrus induced by adrenalectomy in rats.

Testosterone (T), dihydrotestosterone (DHT), 3alpha-diol (5alpha-androstane-3alpha,17beta-diol), or vehicle was administered daily to gonadectomized, adrenalectomized male Long-Evans rats. Four days after adrenalectomy (ADX), animals were tested for inhibitory avoidance. Vehicle-treated rats had shorter latencies than 3alpha-diol-treated rats and non-corticosterone-depleted rats. All three androgens significantly reduced the number of pyknotic cells in corticosterone-depleted rats. Neurosteroids may mediate androgens' functional and morphological neuroprotective effects.