• Archives of Obesity and Metabolism
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• v.3 no.1
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• pp.35-42
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• 2024

Serotonin, a biogenic amine widely found in many organisms, functions as both a neurotransmitter and hormone. Although serotonin is involved in various physiological processes, this study aimed to review its role in energy metabolism. Given that serotonin cannot cross the blood-brain barrier and is synthesized by two different isoforms of tryptophan hydroxylase in the central nervous system (CNS) and peripheral tissues, it is reasonable to assume that serotonin in the CNS and peripheral tissues functions independently. Recent studies have demonstrated how serotonin influences energy metabolism in metabolic target organs such as the intestines, liver, pancreas, and adipose tissue. In summary, serotonin in the CNS induces satiety and appetite suppression, stimulates thermogenesis, and reduces body weight. Conversely, serotonin in the periphery increases intestinal motility, stimulates gluconeogenesis in the liver, suppresses glucose uptake by hepatocytes, promotes fat uptake by liver cells, stimulates insulin secretion while suppressing glucagon secretion in the pancreatic islets, promotes lipogenesis in white adipose tissue, inhibits lipolysis and browning of white adipose tissue, and suppresses thermogenesis in brown adipose tissue, thereby storing energy and increasing body weight. However, considering that most experimental results were obtained using mice and conducted under specific nutritional conditions, such as high-fat diets, whether serotonin acts in the same way in humans, whether it will act similarly in individuals with normal versus obese weights, and whether its effects vary depending on the type of food consumed, remain unknown.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.162-167
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• 1997

There is no doubt that dopamine plays a critical role in the etiopathogenesis of schizophrenia. However, there appeared some limitations in explaining the complex phenomena of schizophrenia. Recent research data suggest that dysfunction in serotonergic system may be involved. Before the dopamine hypothesis of schizophrenia became established, the interest in serotonin(5-hydroxytryptamine, 5-HT) as an etiological substrate of this illness occurred. Recently the importance and extent of 5-HT's involvement in the pathophysiology and mechanism of action of antipsychotic drug is actively investigated. In recent years, therapeutic success of clozapine and risperidones has increased attention on the interaction between the 5-HT and dopamine systems in schizophrenia. This led to the concept of serotonin-dopamine antagonist for antipsychotics. The authors review the evidence for the role of 5- HT in schizophrenia and serotonin-dopamine interaction.

• YAKHAK HOEJI
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• v.35 no.4
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• pp.326-331
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• 1991

Brain serotonin and its utilization was investigated on stressed rats after feeding high tryptophan diet for a month. High tryptophan fed rats displayed significantly higher level of serum tryptophan, brain tryptophan, serotonin (5-hydroxytryptamine; 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) than the control diet fed rats. When rats were treated with 3 hour immobilization (IMMB) stress, serotonin turnover was slightly increased, but not statistically significant, in control diet group rats. However in high tryptophan diet rats, 3 hr IMMB stress resulted in statistically significantly (p<0.05) decreased the serum tryptophan, brain tryptophan and 5-HT level. The concentration of 5-HIAA was significantly increased indicating accelerated utilization of the brain 5-HT of the high trp. fed rat. The utilization pattern of the serotonin was found to be similar among young and adult rats. Rats on a tryptophan enriched diet displayed higher coping ability to the stress as they exhibited smaller increment of corticosterone level. A possble involvement of opioid system was suggested in serotonin utilization by measuring total $^{3}$[H]-naloxone binding in brain.

• Korean Journal of Biological Psychiatry
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• v.11 no.2
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• pp.110-116
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• 2004

Objectives:Recently, polymorphisms of several serotonin genes have been suggested to be associated with suicide, but the results are still unclear. We examined whether the T102C polymorphisms of the serotonin 2A receptor gene and the G861C polymorphisms of the serotonin 1B receptor gene were associated with suicidal behavior using drug intoxication. Methods:The subjects were 52 patients who visited emergency room with suicidal behaviors. Fifty controls were selected from healthy volunteers matched for sex and age to the suicide subjects. The polymorphisms were analyzed with TaqMan$^{(R)}$ assay using primers based on previous studies. Results:The T102C polymorphism of the serotonin 2A receptor gene showed no significant difference between the suicidal attempters and controls in both genotype and allele frequency analyses(p=0.179 and p=0.422, respectively). There was no statistically significant difference between the suicidal attempters and the controls in the G861C polymorphism of the serotonin 1B receptor gene and any significant effect of the genotype distributions or the allele frequencies was not observed(p=0.092 and p=0.987, respectively). Conclusion:These findings suggest that the T102C polymorphism in serotonin 2A receptor gene and the G861C polymorphism in serotonin 1B receptor gene are not related to the susceptibility to suicide attempts using drugs. To clarify the genetic influences of the serotonergic system on suicidal behavior, the polymorphisms of other candidate genes in the serotonergic system should be studied with larger numbers of subjects.

• The Korean Journal of Physiology
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• v.25 no.2
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• pp.133-146
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• 1991

In order to elucidate systematically the effects of serotonin on gastric motility of guinea-pig, the contractile and electrical responses to serotonin were recorded using four kinds of muscle strips prepared from antral circular, antral longitudinal, fundic circular, and fundic longitudinal muscles. Experiments were performed using various methods including isometric contraction recording, transmural electrical field stimulation, junction potential recording, intracellular microelectrode technique, and partition stimulation method. The results were as follows: 1) The effect of serotonin on spontaneous contractions was inhibitory in the circular muscle strips of the antrum and fundus, while it was excitatory in the longitudinal muscle strips of the antrum and fundus. Serotonin changed mainly phasic contractions of both the circular and longitudinal muscle strips in the antrum, while it changed mainly tonic contractions of both the circular and longitudinal muscle strips in the fundus. 2) On the contractions induced by transmural nerve stimulation, serotonin decreased the amplitude in the circular muscle strips of the antrum, but it increased them in the other three groups of muscle strips(antral longitudinal, fundic circular, and fundic longitudinal). 3) On the contractions induced by direct muscle stimulation, serotonin decreased the amplitude in the circular muscle strips of the antrum and fundus. 4) In the fundic circular muscle strips serotonin potentiated excitatory junction potentials (EJPs), and in the antral circular muscle strips it evoked EJPs after inhibitory junction potentials(IJPS). 5) In the antral circular muscle strips serotonin did not affect the slow wave even at the disappearance of spontaneous contractions. On the contrary it increased the amplitude of the slow wave, when the spike component was potentiated and the second component was inhibited. 6) In the antral circular muscle strips the membrane potential was slightly hyperpolarized, but the membrane resistance was not changed. From the above results following conclusions could be made. 1) Serotonin inhibits spontaneous contractions of the circular muscle layer and it increases those of the longitudinal one, irrespective of the gastric region. 2) In the guinea-pig stomach there exists a serotoninergic facilitatory neuromodulation system which exerts its effect on cholinergically mediated contraction. 3) The excitation-contraction decoupling was observed in the effect of serotonin.

• Archives of Pharmacal Research
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• v.11 no.4
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• pp.301-307
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• 1988

Relationship between the maintenance of hypertension and central serotonergic nervous system activity in opontaneously hypertensive rats (SHR) was studied. Serotonin turnover-rates were measured in 5 brain areas as an index of serotonergic neuronal activity and compared at the ages of 14 weeks in two types of animals; (1) spontaneously hypertensive rats (SHR) (2) normotensive wistar kyoto rats (WKY). In 14-week old SHR, central serotonin turnover rate was significantly lower in telencephalon, hypothalamus/thalamus and midbrain than normotensive rat, but significantly higher in cerebellum. There were no significant differences between serotonin turnover rate in pons/medulla of SHR and that of normotensive rat. THese data suggest that the abnormally lower turnover rates of serotonin in telencephalon, hypothalamus/thalamus and midbrain may be one of the underlying neuronal factors for manifestation of hypertension in SHR.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.11.1-11.9
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• 2018

Estrogen has diverse effects on cardiovascular function, including regulation of the contractile response to vasoactive substances such as serotonin. The serotonin system recently emerged as an important player in the regulation of vascular tone in humans. However, hyperreactivity to serotonin appears to be a critical factor for the pathophysiology of hypertension. In this study, we examined the modulatory mechanisms of estrogen in serotonin-induced vasoconstriction by using a combinatory approach of isometric tension measurements, molecular biology, and patch-clamp techniques. $17{\beta}$-Estradiol (E2) elicited a significant and concentration-dependent relaxation of serotonin-induced contraction in deendothelialized aortic strips isolated from male rats. E2 triggered a relaxation of serotonin-induced contraction even in the presence of tamoxifen, an estrogen receptor antagonist, suggesting that E2-induced changes are not mediated by estrogen receptor. Patch-clamp studies in rat arterial myocytes showed that E2 prevented Kv channel inhibition induced by serotonin. Serotonin increased Src activation in arterial smooth muscle required for contraction, which was significantly inhibited by E2. The estrogen receptor-independent inhibition of Src by E2 was confirmed in HEK293T cells that do not express estrogen receptor. Taken together, these results suggest that estrogen exerts vasodilatory effects on serotonin-precontracted arteries via Src, implying a critical role for estrogen in the prevention of vascular hyperreactivity to serotonin.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.188-193
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• 1997

Along with psychosocial factors of suicide, biological backgrounds of suicide are explored by extensive works mostly on biological markers, neurobiological models, genetic bases, and relationships with aggression and violence. The biology of suicide confers on neurotransmitters in central nervous system exploring metabolites, receptor binding affinities, neuroendocrine challenge tests in brain, cerebrospinal fluid, blood and etc. The major concerns with suicide are focused mainly on serotonin system : low CSF 5-HIAA concentration, higher $5-HT_2$ receptor binding, and blunt prolactin response to fenfluramine. Postmortem study, in vivo study, genetic contributions, and some other issues such as suicidal methods, serum cholesterol, alcohol, and selective serotonin reuptake inhibitors are reviewed and discussed.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.88-95
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• 2001

(+)-Methamphetamine (METH) is a psychostimulant, which has been the most popular abused drug in Korea. The rewarding mechanism in METH abuse has been reported to be mediated by dopaminergic system. Recently, it has been reported that dopamine releaser (phentermine) plays a dominant role in the discriminative stimulus effects of METH, whereas 5-HT releaser (fenfluramine) can strongly modify METH self-administration. The present study is designed to assess the behavioral changes and the changes of the serotonin receptors in the brains of rats administered repeated of self-administered METH. The repeated administration of 1.0 mg/kg/day METH for 12 days increased locomotor activities, and there was no difference between i.v. and i.p. treatment. Rats had actively acquired METH self-administration for 3 weeks at 0.1 or 0.2 mg/kg/injection. Whereas, it was taken few days to acquire sucrose pellet self-administration. The binding of [$^3$H]-8-hydroxy-DPAT (5-H $T_{1A}$ receptors) and [$^3$H]-5-carboxytryptamine (5-H $T_{1B}$ receptors) to brain sections was examined. Both passive administration and self-administration of METH did not change significantly the serotonin receptors levels in hippocampus, striatum and nucleus accumbens. These results suggest that serotonin receptors may not change in the acquisition period of METH self-administration, and we are trying to investigate the serotonin receptors levels of brain in rats maintained of METH self-administration.n.n.

• The Korean Journal of Pain
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• v.33 no.4
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• pp.318-325
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• 2020

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. Methods: Sprague-Dawley rats (weight 150-180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. Results: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. Conclusions: NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.