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Introduction: Aggression and self-harm disproportionately occur in youths preoccupied with social status tracking. These pathological conditions are linked to a serotonin (5-HT) deficit in the brain. Ablation of 5-HT biosynthesis by tryptophan hydroxylase 2 knockout (TPH2-KO) increases aggression in rodents. Remarkably, deletion of the trace amine-associated receptor 1 (TAAR1) results in the same consequences. Unlike the nuanced dynamics of social status cues in young people, the social ranks of rats mainly advance when they dominate larger opponents in combat. Methods: This study explored whether the potent TAAR1 agonist RO5263397 reduces aggression caused by 5-HT depletion, and whether social rank advancement motivates this aggression. The resident-intruder paradigm was applied with larger and smaller intruders to evaluate whether social rank advancement motivates aggressive behaviors in TPH2-KO rats. Results: When a smaller intruder was introduced, 5-HT-deficient rats did not differ from wild type littermates. However, when the intruders were larger, the mutants extended their aggressive efforts, refusing to submit. Importantly, RO5263397 selectively abolished this abnormal form of aggression in TPH2-KO rats. Discussion: Results supported social rank advancement as the main incentive. These data also suggest that TAAR1 is a promising target for the development of new treatments for aggression; independent data also support this conclusion. [ABSTRACT FROM AUTHOR]

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It has been shown that chronic restraint stress (CRS) increases adrenal 5-HT levels and turnover through a mechanism that appears unrelated to tryptophan hydroxylase (TPH). In the present study we re-analyzed the effects of CRS (20 min/day) for 14 days relative to control (CTRL) conditions on TPH expression, distribution, and activity in rat adrenal glands. On day 15, adrenal glands were collected for TPH1 and TPH2 immunohistochemistry, Western blot, and RT-PCR; TPH activity was estimated by quantification of 5-hydroxytryptophan (5-HTP) and, indirectly, through measurement of 5-HT and 5-hydroxindolacetic acid (5-HIAA) levels and turnover (5-HIAA/5-HT ratio) by HPLC. TPH expression and activity in the dorsal raphe nucleus (DRN) were also determined for comparison. TPH1 and TPH2 immunostaining was observed in the adrenal medulla, and measurable levels of TPH1 and TPH2 protein and mRNA were detected in rat adrenal glands from CTRL animals. CRS exposure noticeably increased TPH2- but not THP1-immunostaining in the medulla and the outer adrenocortical areas of left (LAG) but not of right adrenal glands (RAG). In addition, CRS exposure increased TPH2 protein and mRNA levels in LAG; however, both measures decreased in DRN. Finally, CRS treatment produced an increase and a decrease of TPH activity and 5-HT turnover in LAG and DRN, respectively. Results indicate that TPH is indeed expressed in rat adrenal glands. Exposure to CRS upregulates TPH2 in LAG, while inducing downregulation of it in the DRN. Then, the increased levels of 5-HT in LAG from CRS-exposed animals likely results from TPH2-mediated synthesis. • Tryptophan hydroxylase (TPH) is expressed in rat adrenal glands. • TPH1 and TPH2 expression seems to occur in the adrenal medulla. • Chronic restraint stress increases TPH2 expression and activity in rat adrenal glands. • Chronic restraint stress decreases TPH2 expression and activity in the dorsal raphe nucleus [ABSTRACT FROM AUTHOR]

Since its discovery in 1984, the monoamine serotonin (5-HT) has been recognized for its critical role as a neuromodulator in both the central and peripheral nervous systems. Recent research reveals that serotonin also significantly influences various neuronal activities. Historically, it was believed that peripheral serotonin, produced by tryptophan hydroxylase in intestinal cells, functioned primarily as a hormone. However, new insights have expanded its known roles, necessitating advanced detection methods. Biosensors have emerged as indispensable tools in biomedical diagnostics, enabling the rapid and minimally invasive detection of target analytes with high spatial and temporal resolution. This review summarizes the progress made in the past decade in developing optical and electrochemical biosensors for serotonin detection. We evaluate various sensing strategies that optimize performance in terms of detection limits, sensitivity, and specificity. The study also explores recent innovations in biosensing technologies utilizing surface-modified electrodes with nanomaterials, including gold, graphite, carbon nanotubes, and metal oxide particles. Applications range from in vivo studies to chemical imaging and diagnostics, highlighting future prospects in the field. [Display omitted] [ABSTRACT FROM AUTHOR]