Chronic elevations in glucocorticoids can decrease the production and survival of new cells in the adult brain. In rat hippocampus, supraphysiological doses of dehydroepiandrosterone (DHEA; a sex steroid precursor synthesized in the gonads, adrenals, and brain) have antiglucocorticoid properties. With male song sparrows (Melospiza melodia), we examined the effects of physiological doses of corticosterone, the primary circulating glucocorticoid in birds, and DHEA on adult neuroplasticity. We treated four groups of nonbreeding sparrows for 28 days with empty (control), corticosterone, DHEA, or corticosterone + DHEA implants. Subjects were injected with BrdU on days 3 and 4. In HVC, a critical song control nucleus, corticosterone and DHEA had independent, additive effects. Corticosterone decreased, whereas DHEA increased, HVC volume, NeuN(+) cell number, and BrdU(+) cell number. Coadministration of DHEA completely reversed the neurodegenerative effects of chronic corticosterone treatment. In an efferent target of HVC, the robust nucleus of the arcopallium (RA), DHEA increased RA volume, but this effect was blocked by coadministration of corticosterone. There were similar antagonistic interactions between corticosterone and DHEA on BrdU(+) cell number in the hippocampus and ventricular zone. This is the first report on the effects of corticosterone treatment on the adult song control circuit, and HVC was the most corticosterone-sensitive song nucleus examined. In HVC, DHEA is neuroprotective and counteracts several pronounced effects of corticosterone. Within brain regions that are particularly vulnerable to corticosterone, such as the songbird HVC and rat hippocampus, DHEA appears to be a potent native antiglucocorticoid.

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