Abstract
Although it is well-known that defective signaling of the 5-HT system in the brain and stressful stimuli can cause psychological disorders, their combined effects on male–male aggression and sexual attractiveness remain unknown. Our research aimed at examining such effects using tryptophan hydroxylase 2 (Tph2) knockout male mice vs. a rat- or rat scent-based chronic stress model. Tph2+/+ and Tph2−/− male mice were placed individually into the rat home cage (rat), a cage containing soiled rat bedding (rat scent) or a cage containing fresh bedding (control) for 5 h every other day for 56 consecutive days. In Tph2+/+ male mice, rat-exposure decreased male–male aggression and sexual attractiveness of urine odor relative to either rat scent-exposure or control; and rat scent-exposure decreased aggression rather than sexual attractiveness of urine odor compared with control. However, such dose-dependent and long-lasting behavioral inhibitory effects vanished in Tph2−/− male mice. RT-PCR assay further revealed that putative regulatory genes, such as AR, ERα and GluR4 in the prefrontal cortex, and TrkB-Tc and 5-HTR1A in the hippocampus, were down-regulated at the mRNA level in either rat- or rat scent-exposed Tph2+/+ male mice, but partially in the Tph2−/− ones. Hence, we suggest that the dose-dependent and long-lasting inhibitory effects of chronic predator exposure on male–male aggression, sexual attractiveness of urine odor, and mRNA expression of central regulatory genes might be mediated through the 5-HT system in the brain of male mice.
Highlights
Rodents rely heavily on chemical senses to detect potential predators and minimize predation risk in natural habitats (Herman and Valone, 2000; Dielenberg and McGregor, 2001; Zhang et al, 2008)
Two-choice tests unraveled that the urine odor from either rat scent-exposed tryptophan hydroxylase 2 (Tph2) +/+ males [Figure 2A, Wilcoxon rank sum test, median 3.390 vs. median 1.280, Z = −2.073, N = 15, P = 0.038] or control Tph2 +/+ males [Figure 2A, Wilcoxon rank sum test, median 4.780 vs. median 3.495, Z = −2.103, N = 14, P = 0.035] induced higher attraction of Tph2 +/+ females than that from rat-exposed Tph2 +/+ males
Two-choice tests revealed that the urine odor between any two groups of Tph2 −/− males induced no apparent differences in attraction of Tph2 +/+ females (Figure 2B)
Summary
Rodents rely heavily on chemical senses to detect potential predators and minimize predation risk in natural habitats (Herman and Valone, 2000; Dielenberg and McGregor, 2001; Zhang et al, 2008). The presence of predators or their chemical cues often have non-lethal, but negative, effects on the behavioral, and neurophysiological states of rodents (Dielenberg and McGregor, 2001; Zhang et al, 2003; Adamec et al, 2004; Apfelbach et al, 2005). Chronic exposure of rodents to a predator or its chemical cues can enhance anxiety-like behaviors and decrease aggression levels (Francis, 1988; Blanchard et al, 2001; Zhang et al, 2003). Previous studies have found that the effect of predator scent-exposure on rodent anxiety and risk assessment fall between controls and those exposed to a predator (Adamec et al, 2004, 2006b). Rat- and rat scent-exposure are graded predator stress to mice
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