Testosterone and its metabolites modulate 5HT1A and 5HT1B agonist effects on intermale aggression

Serotonin (5-HT) is an indirect modulator of the electric organ discharge (EOD) in the weakly electric gymnotiform fish, Brachyhypopomus pinnicaudatus. Injections of 5-HT enhance EOD waveform "masculinity", increasing both waveform amplitude and the duration of the second phase. This study investigated the pharmacological identity of 5-HT receptors that regulate the electric waveform and their effects on EOD amplitude and duration. We present evidence that two sets of serotonin receptors modulate the EOD in opposite directions. We found that the 5HT 1A R agonist 8-OH-DPAT diminishes EOD duration and amplitude while the 5HT 1A R antagonist WAY100635 increases these parameters. In contrast, the 5HT 2 R agonist α-Me-5-HT increases EOD amplitude but not duration, yet 5-HT-induced increases in EOD duration can be inhibited by blocking 5HT 2A/2C -like receptors with ketanserin. These results show that 5-HT exerts bi-directional control of EOD modulations in B. pinnicaudatus via action at receptors similar to mammalian 5HT 1A and 5HT 2 receptors. The discordant amplitude and duration response suggests separate mechanisms for modulating these waveform parameters. KeywordsSerotonin; Electric organ discharge; Communication signal; 5HT 1A receptor; 5HT 2 receptor; Social interaction; Dominance hierarchy Serotonin (5-HT) is a neuromodulator so ubiquitous that hardly any physiological function or behavior is free from its direct or indirect effects. As a result, a full account of neuroendocrine control of behavior requires a thorough assessment of 5-HT's function across a wide range of circumstances, even as the pervasive presence of 5-HT in the nervous system complicates unambiguous assessment of its functions. Particularly, serotonin is involved in the regulation of diametrically opposed behaviors, aggression and subordinance (Summers and Winberg, 2006). Serotonin activity rises in both dominant and subordinate males but rapidly returns to baseline in dominants while it stays chronically high in subordinates (Overli et al., 1999;Summers and Winberg, 2006). Prior social defeat or success during aggressive interactions affects future aggressive behaviors and the activity of the serotonergic system (Winberg et al., 1992;Winberg et al., 1997b). Furthermore, social experience affects the regulatory effect of serotonin on dominant behaviors via serotonin receptors 1A and 2A (Yeh et al., 1996). Pharmaceutical 5HT 1A agonists inhibit aggression or induce submissive behaviors in a wide range of non-mammalian vertebrates including green anoles (Deckel and Fuqua, 1998), Arctic charr (Hoglund et al., 2002;Winberg and Nilsson, 1993) Bell et al., 2007). In addition, 5HT 1A receptors operate as both postsynaptic receptors and as pre-synaptic autoreceptors to either suppress or stimulate stress responses in teleosts as they do in mammals (Hoglund et al., 2002). Despite the functionally and anatomically conserved nature of the serotonin system in vertebrates (Parent et al., 1984) and the abundance of data indicating a role for 5HT ...

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Opposing actions of 5HT1A and 5HT2-like serotonin receptors on modulations of the electric signal waveform in the electric fish Brachyhypopomus pinnicaudatus

Allee

Markham

Salazar

et al. 2008

“…Laboratory studies reveal that the neural circuit for intermale aggression involves several brain regions, including the amygdala, hippocampus, anterior hypothalamus, septum, anterior cingulated cortex, insular cortex, prefrontal cortex, ventral striatum, and interconnections (Nelson and Chiavegatto, 2001). Both steroid hormone and neurotransmitter receptors are densely populated on neurons in these brain regions and contribute to the expression of aggression in vertebrates (Simon et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Among all major neurotransmitters, serotonin (5-HT) is most often associated with the expression of intermale aggression (Miczek and Fish, 2005;Nelson and Chiavegatto, 2001;Simon et al, 1998). Reduced 5-HT activity facilitates, whereas increased 5-HT neurotransmission decreases, intermale aggression (Olivier and Mos, 1990;Simon et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Elevated testosterone and reduced 5-HIAA concentrations are associated with wounding and hantavirus infection in male Norway rats

Easterbrook

Kaplan

Glass

et al. 2007

Among rodents that carry hantaviruses, males are more likely to engage in aggression and to be infected than females. One mode of hantavirus transmission is via the passage of virus in saliva during wounding. The extent to which hantaviruses cause physiological changes in their rodent host that increase aggression and, therefore, virus transmission has not been fully documented. To assess whether steroid hormones and neurotransmitters contribute to the correlation between aggression and Seoul virus infection, Norway rats were trapped in Baltimore, Maryland and wounding, infection status, steroid hormones, and concentrations of neurotransmitters, including norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenol acetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) in select brain regions were examined. Older males and males with high-grade wounds were more likely to have anti-Seoul virus IgG and viral RNA in organs than either juveniles or adult males with less severe wounds. Wounded males had higher circulating testosterone, lower hypothalamic 5-HIAA, and lower NE in the amygdala than males with no wounds. Infected males had higher concentrations of testosterone, corticosterone, NE in the hypothalamus, and DOPAC in the amygdala than uninfected males, regardless of wounding status. In the present study, wounded males that were infected with Seoul virus had elevated testosterone and reduced 5-HIAA concentrations, suggesting that these neuroendocrine mechanisms may contribute to aggression and the likelihood of transmission of hantavirus in natural populations of male Norway rats.

“…Exposure to androgens early in life affects the expression and distribution of 5-HT receptor subtypes (Simon et al, 1998;Sumner and Fink, 1998;Nelson and Chiavegatto, 2001). Both testosterone and estradiol increase the levels of 5-HT 2A receptor mRNA and binding site densities in the brains of male rats (Sumner and Fink, 1998).…”

Section: -Ht and Female Aggressionmentioning

confidence: 99%

Interaction of nitric oxide and serotonin in aggressive behavior

Chiavegatto

Nelson

2003

Nitric oxide (NO) modulates many behavioral and neuroendocrine responses. Genetic or pharmacological inhibition of the synthetic enzyme that produces NO in neurons evokes elevated and sustained aggression in male mice. Recently, the excessive aggressive and impulsive traits of neuronal NO synthase knockout (nNOS Ϫ/Ϫ ) mice were shown to be caused by reductions in serotonin (5-HT) turnover and deficient 5-HT 1A and 5-HT 1B receptor function in brain regions regulating emotion. The consistently high levels of aggression observed in nNOS Ϫ/Ϫ mice could be reversed by 5-HT precursors and by treatment with specific 5-HT 1A and 5-HT 1B receptor agonists. The expression of the aggressive phenotype of nNOS Ϫ/Ϫ knockout mice requires isolated housing prior to testing. The effects of social factors such as housing condition and maternal care can affect 5-HT and aggression, but the interaction among extrinsic factors, 5-HT, NO, and aggression remains unspecified. Taken together, NO appears to play an important role in normal brain 5-HT function and may have significant implications for the treatment of psychiatric disorders characterized by aggressive and impulsive behaviors.