Testosterone decrease does not play a major role in the suppression of hippocampal cell proliferation following social defeat stress in rats

Abstract

Stress of social defeat in rodents is known to have a strong and long-lasting effect on brain, physiology and behavior, which bears similarities with certain human stress related psychopathologies. Previous experiments in this lab showed that social defeat stress suppresses testosterone secretion and causes a lasting desensitization of the serotonergic 5-HT(1A) receptors. Testosterone supplementation in socially stressed tree shrews prevented a decrease in hippocampal 5-HT(1A) receptor binding. These receptors are hypothesized to play an important role in neurogenesis in this brain structure. We designed the present experiment to test if social defeat reduces hippocampal cell proliferation and neurogenesis in rats and if testosterone supplementation can prevent this reduction. The results indicate that repeated social defeat stress on 5 successive days induces a significant drop in plasma testosterone levels in male rats and suppresses hippocampal cell proliferation 24h and 3weeks after the end of the stress period. Testosterone supplementation prevented the social stress induced drop in plasma testosterone levels. The hormone supplementation also reduced the negative effect of stress on hippocampal BrdU labeling at 3weeks post-defeat. This effect was, however, rather weak and was caused by the tendency of the hormone in itself to suppress proliferation and the failure to fully recover the proliferation rate. Survival of dentate gyrus cells that either proliferated prior to the stress period or 24h after the last defeat was not affected by the social defeats. Thus the stress-induced lowering of hippocampal cell proliferation is not likely to be caused by transient inhibition of testosterone secretion during social stress.