Oxytocin stimulates adult neurogenesis even under conditions of stress and elevated glucocorticoids

Abstract

Oxytocin has been linked to social behavior, including social recognition, pair bonding and parenting, but its potential role in promoting neuronal growth has not been investigated. We show here that oxytocin, but not vasopressin, stimulates both cell proliferation and adult neurogenesis in the hippocampus of rats. Oxytocin is also capable of stimulating adult neurogenesis in rats subjected to glucocorticoid administration or cold water swim stress. These findings suggest that oxytocin stimulates neuronal growth and may protect against the suppressive effects of stress hormones on hippocampal plasticity.

Figure 1. Peripheral oxytocin administration enhances cell proliferation in the ventral dentate gyrus

Adult male rats received an i.p. injection of oxytocin (OT) or an equal volume of saline. All rats were injected with BrdU 30 min later and perfused after 2 hr. Rats treated with 1mg/kg OT had a greater number of BrdU-labeled cells in the ventral, but not dorsal, dentate gyrus compared to those treated with saline or 10 mg/kg OT. Bars represent mean ± SEM, *p < 0.05. Photomicrographs show more BrdU-labeled cells (brown cells) in the ventral dentate gyrus of rats treated with OT. Scale bar, 10 um.

Figure 2. Peripheral OT administration does not alter the density of BrdU-labeled cells in the SVZ

The density of BrdU-labeled cells in the SVZ of rats treated with 1 mg/kg OT or 10 mg/kg OT did not differ from saline-treated rats. Bars represent mean ± SEM. Photomicrographs show BrdU-labeled cells in the SVZ of saline and oxytocin treated rats. Scale bar, 10 um.

Figure 3. Chronic peripheral oxytocin enhances adult neurogenesis

Rats received an i.p. injection of OT (1mg/kg) or an equal volume of saline once daily for 7 consecutive days. All animals were injected with BrdU 30 min after the last injection and perfused after a 3 wk survival. (a) Chronic OT increased the number of BrdU-labeled cells in the ventral, but not dorsal, dentate gyrus. Bars represent mean ± SEM, *p < 0.05. At this time, most BrdU-labeled cells (red) in the saline and OT groups were co-labeled with (b) the mature neuronal marker NeuN (green) but not with (c) the astroglial marker GFAP (green). Scale bar, 10 μm.

Figure 4. Central administration of oxytocin enhances cell proliferation

Adult male rats received hippocampal injections of OT (1ng/μL) in one hemisphere or an equal volume of saline into the other hemisphere. All animals were injected with BrdU 30 min later and perfused after a 2 hr survival. The hemisphere treated with OT had a greater number of BrdU-labeled cells in the ventral dentate gyrus compared to the saline-treated hemisphere. The number of BrdU-labeled cells in the dorsal dentate gyrus did not differ between the saline and OT treated hemispheres. Bars represent mean ± SEM, *p < 0.05. Photomicrographs show more BrdU-labeled cells (brown cells) in the ventral dentate gyrus of rats treated with OT. Scale bar, 10 um.