Social stress increases plasma cortisol and reduces forebrain cell proliferation in subordinate male zebrafish (Danio rerio)

Abstract

Many animals, including zebrafish (Danio rerio), form social hierarchies through competition for limited resources. Socially subordinate fish may experience chronic stress, leading to prolonged elevation of the glucocorticoid stress hormone cortisol. As elevated cortisol levels can impair neurogenesis, the present study tested the hypothesis that social stress suppresses cell proliferation in the telencephalon of subordinate zebrafish via a cortisol-mediated mechanism. Cell proliferation was assessed using incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU). After 48 and 96 h of social interaction, subordinate male zebrafish exhibited elevated plasma cortisol concentrations and significantly lower numbers of BrdU⁺ cells in the dorsal but not ventral regions of the telencephalon compared with dominant or group-housed control male fish. After a 2 week recovery in a familiar group of conspecifics, the number of BrdU⁺ cells that co-labelled with a neuronal marker (NeuN) was modestly reduced in previously subordinate male fish, suggesting that the reduction of cell proliferation during social stress may result in fewer cells recruited into the neuronal population. In contrast to male social hierarchies, subordinate female zebrafish did not experience elevated plasma cortisol, and the number of BrdU⁺ cells in the dorsal telencephalic area was comparable among dominant, subordinate and group-housed control female fish. Treating male zebrafish with metyrapone, a cortisol synthesis inhibitor, blocked the cortisol response to social subordination and attenuated the suppression of brain cell proliferation in the dorsal telencephalic area of subordinate fish. Collectively, these data support a role for cortisol in regulating adult neurogenesis in the telencephalon of male zebrafish during social stress.

Keywords: Behaviour; Brain; BrdU; Fish; Glucocorticoid; Metyrapone; Neurogenesis; Telencephalon.