Individual differences in the boldness of female zebrafish are associated with alterations in serotonin function.

One of the most prevalent axes of behavioral variation in both humans and animals is risk taking, where individuals that are more willing to take risk are characterized as bold while those that are more reserved are regarded as shy. Brain monoamines (i.e. serotonin, dopamine and noradrenaline) have been found to play a role in a variety of behaviors related to risk taking. Using zebrafish, we investigated whether there was a relationship between monoamine function and boldness behavior during exploration of a novel tank. We found a correlation between serotonin metabolism (5-HIAA:5-HT ratio) and boldness during the initial exposure to the tank in female animals. The DOPAC:DA ratio correlated with boldness behavior on the third day in male fish. There was no relationship between boldness and noradrenaline. To probe differences in serotonergic function in bold and shy fish, we administered a selective serotonin reuptake inhibitor, escitalopram, and assessed exploratory behavior. We found that escitalopram had opposing effects on thigmotaxis in bold and shy female animals: the drug caused bold fish to spend more time near the center of the tank and shy fish spent more time near the periphery. Taken together, our findings indicate that variation in serotonergic function has sex-specific contributions to individual differences in risk-taking behavior.

Alterations in the brain serotonin system and serotonin-regulated behavior during aging in zebrafish males and females.

The brain serotonin (5-HT) system performs a neurotrophic function and supports the plasticity of the nervous system, while its age-related changes can increase the risk of senile neurodegeneration. Zebrafish brain is highly resistant to damage and neurodegeneration due to its high regeneration potential and it is a promising model object in searching for molecular factors preventing age-related neurodegeneration. In the present study alterations in 5-HT-related behavior in the home tank and the novel tank diving test, as well as 5-HT, 5-HIAA levels, tryptophan hydroxylase (TPH), monoamine oxidase (MAO) activity and the expression of genes encoding TPH, MAO, 5-HT transporter and 5-HT receptors in the brain of 6, 12, 24 and 36 month old zebrafish males and females are investigated. Marked sexual dimorphism in the locomotor activity in the novel tank test is revealed: females of all ages move slower than males. No sexual dimorphism in 5-HT-related traits is observed. No changes in 5-HT and 5-HIAA levels in zebrafish brain during aging is observed. At the same time, the aging is accompanied by a decrease in the locomotor activity, TPH activity, tph2 and htr1aa genes expression as well as an increase in the MAO activity and slc6a4a gene expression in their brain. These results indicate that the brain 5-HT system in zebrafish is resistant to age-related alterations.

Rebound activation of 5-HT neurons following SSRI discontinuation.

Cessation of therapy with a selective serotonin (5-HT) reuptake inhibitor (SSRI) is often associated with an early onset and disabling discontinuation syndrome, the mechanism of which is surprisingly little investigated. Here we determined the effect on 5-HT neurochemistry of discontinuation from the SSRI paroxetine. Paroxetine was administered repeatedly to mice (once daily, 12 days versus saline controls) and then either continued or discontinued for up to 5 days. Whereas brain tissue levels of 5-HT and/or its metabolite 5-HIAA tended to decrease during continuous paroxetine, levels increased above controls after discontinuation, notably in hippocampus. In microdialysis experiments continuous paroxetine elevated hippocampal extracellular 5-HT and this effect fell to saline control levels on discontinuation. However, depolarisation (high potassium)-evoked 5-HT release was reduced by continuous paroxetine but increased above controls post-discontinuation. Extracellular hippocampal 5-HIAA also decreased during continuous paroxetine and increased above controls post-discontinuation. Next, immunohistochemistry experiments found that paroxetine discontinuation increased c-Fos expression in midbrain 5-HT (TPH2 positive) neurons, adding further evidence for a hyperexcitable 5-HT system. The latter effect was recapitulated by 5-HT1A receptor antagonist administration although gene expression analysis could not confirm altered expression of 5-HT1A autoreceptors following paroxetine discontinuation. Finally, in behavioural experiments paroxetine discontinuation increased anxiety-like behaviour, which partially correlated in time with the measures of increased 5-HT function. In summary, this study reports evidence that, across a range of experiments, SSRI discontinuation triggers a rebound activation of 5-HT neurons. This effect is reminiscent of neural changes associated with various psychotropic drug withdrawal states, suggesting a common unifying mechanism.

The High-Precision Liquid Chromatography with Electrochemical Detection (HPLC-ECD) for Monoamines Neurotransmitters and Their Metabolites: A Review.

This review highlights the advantages of high-precision liquid chromatography with an electrochemical detector (HPLC-ECD) in detecting and quantifying biological samples obtained through intracerebral microdialysis, specifically the serotonergic and dopaminergic systems: Serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), 3-metoxytryptamin (3-MT) and homovanillic acid (HVA). Recognized for its speed and selectivity, HPLC enables direct analysis of intracerebral microdialysis samples without complex derivatization. Various chromatographic methods, including reverse phase (RP), are explored for neurotransmitters (NTs) and metabolites separation. Electrochemical detector (ECD), particularly with glassy carbon (GC) electrodes, is emphasized for its simplicity and sensitivity, aimed at enhancing reproducibility through optimization strategies such as modified electrode materials. This paper underscores the determination of limits of detection (LOD) and quantification (LOQ) and the linear range (L.R.) showcasing the potential for real-time monitoring of compounds concentrations. A non-exhaustive compilation of literature values for LOD, LOQ, and L.R. from recent publications is included.