• Archives of Pharmacal Research
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• v.22 no.2
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• pp.113-118
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• 1999

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic $5-HT_{2}$ receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompeti-tive (MI-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsyaptic $5-HT_{2}$receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin $5-HT_{2}$receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the poststynaptic $5-HT_{2}$ receptors.

• BMB Reports
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• v.56 no.10
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• pp.527-536
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• 2023

Serotonin receptors, also known as 5-HT receptors, belong to the G protein-coupled receptors (GPCRs) superfamily. They mediate the effects of serotonin, a neurotransmitter that plays a key role in a wide range of functions including mood regulation, cognition and appetite. The functions of serotonin are mediated by a family of 5-HT receptors including 12 GPCRs belonging to six major families: 5-HT₁, 5-HT₂, 5-HT₄, 5-HT₅, 5-HT₆ and 5-HT₇. Despite their distinct characteristics and functions, these receptors' subtypes share common structural features and signaling mechanisms. Understanding the structure, functions and pharmacology of the serotonin receptor family is essential for unraveling the complexities of serotonin signaling and developing targeted therapeutics for neuropsychiatric disorders. However, developing drugs that selectively target specific receptor subtypes is challenging due to the structural similarities in their orthosteric binding sites. This review focuses on the recent advancements in the structural studies of 5-HT receptors, highlighting the key structural features of each subtype and shedding light on their potential as targets for mental health and neurological disorders (such as depression, anxiety, schizophrenia, and migraine) drugs.

• Journal of Animal Reproduction and Biotechnology
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• v.38 no.2
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• pp.77-83
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• 2023

Background: Serotonin receptors can be divided into seven different families with various subtypes. The serotonin 1A (5-HT1A) receptor is one of the most abundant subtypes in animal brains. The expression of 5-HT1A receptors in the brain has been reported in various animals but has not been studied in horses. The 5-HT1A receptor functions related to emotions and behaviors, thus it is important to understand the functional effects and distribution of 5-HT1A receptors in horses to better understand horse behavior and its associated mechanism. Methods: Brain samples from seven different regions, which were the frontal, central, and posterior cerebral cortices, cerebellar cortex and medulla, thalamus, and hypothalamus, were collected from six horses. Western blot analysis was performed to validate the cross-reactivity of rabbit anti-5-HT1A receptor antibody in horse samples. Immunofluorescence was performed to evaluate the localization of 5-HT1A receptors in the brains. Results: The protein bands of 5-HT1A receptor appeared at approximately 50 kDa in the frontal, central, and posterior cerebral cortices, cerebellar cortex, thalamus, and hypothalamus. In contrast, no band was observed in the cerebellar medulla. Immunofluorescence analysis showed that the cytoplasm of neurons in the cerebral cortices, thalamus, and hypothalamus were immunostained for 5-HT1A receptors. In the cerebellar cortex, 5-HT1A was localized in the cytoplasm of Purkinje cells. Conclusions: In conclusion, the study suggests that 5-HT and 5-HT1A receptor systems may play important roles in the central nervous system of horses, based on the widespread distribution of the receptors in the horse brain.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4455-4458
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• 2014

Breast cancer is a serious and potentially lethal multi-factor disease among 40-50 aged women in both developed and developing countries. Also, various studies have pointed to roles of neurotransmitters like serotonin in development of cancers, through action on various types of receptors. This study was conducted to evaluate serotonin receptor (5HT2AR and 5HT3AR) genes expression in peripheral blood mononuclear cells (PBMCs) of breast cancer patients in comparison with the healthy people and in the MCF7 cell line. Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total RNA was extracted from PBMCs and MCF-7 cells. and 5HT2AR and 5HT3AR were detected by RT-PCR techniques. Finally, serotonin receptor gene expression variation in breast cancer patients and MCF-7 cells were determined by real time-PCR. This latter indicated significant promotion in expression of 5HT3AR and 5HT2AR in PBMCs in breast cancer patients but expression of 5HT2AR in the MCF-7 cell line was significantly decreased. In conclusion, after performing complimentary tests, determine of gene expression changes in serotonin receptors (5HT2AR and 5HT3AR) may be useful as a new approach in treatment of breast cancer based on use of antagonists.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.355-359
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• 2000

Cocaine induces immediate early gene expression and behavioral changes by blocking dopamine transporters in the terminals of nigrostriatal neurons in the striatum. The pharmacological role of serotonin 2/1C (5HT2/1C) receptors in cocaine-induced expression of zif268 (NGFI-A, egr1 and Krox-24) mRNA, a member of the zinc finger, was investigated using quantitative in situ hybridization histochemistry in vivo. Behavioral alterations induced by cocaine were also monitored in relation with blockade of the receptors. Systemic injection of ritanserin (1 mg/kg, s.c.), a 5HT2/1C receptor antagonist, did not reverse behavioral alterations and zif268 mRNA gene expression induced by 15 mg/kg cocaine, i.p., in the dorsal and ventral striatum. These data indicate that ritanserin-sensitive 5HT2/1C receptors are not necessary for cocaine-induced behavioral alterations and zif268 mRNA gene expression in the striatum.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.267-272
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• 2011

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the $5HT_2$ receptor antagonist ketanserin and the $5-HT_3$ receptor antagonist ondansetron but was inhibited by the 5-$HT_1$ receptor antagonist methysergide and 5-$HT_4$ receptor antagonist GR113808. These results indicate that 5-$HT_1$ and 5-$HT_4$ receptors may mediate the contraction of the 5-HT-induced response and 5-$HT_2$ and 5-$HT_3$ receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.170-170
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• 1998

In order to discover new types of 5-hydroxytryptamine antagonists, we have devoted our attention to investigating naturally occurring compounds having anti-5HT activity in vitro. Recently, ${\gamma}$-mangostin [1,3,6,7-tetrahydroxy-2,8-bis(3-methyl-2-bytenyl)-9H-xanthen-9-one] from the fruit hull of Garcinia mangostana Linn has been shown to be a selective antagonist for 5-hydroxytryptamine$_{2A}$ receptors in smooth muscle and platelets. It is of interesting that y-mangostin which does not have a nitrogen atom, possesses marked 5-$HT_{2A}$ receptor blocking activity. The present study was undertaken to investigate the effects of ${\gamma}$-mangostin on central 5-HT receptors by using animal behavioural models. Intracerebronventricular injection of ${\gamma}$-mangostin (10-40n mol/mouse) inhibited 5-fluoro-${\alpha}$-methyltryptamin (5-FMT) (45 mg kg$^{-1}$, i.p.)-induced head-twitch response in mice in the presence or absence of citalopram (5-HT-uptake inhibitor). Neither the 5-FMT- nor the 8-hydroxy-2-( di-n-propylamino )tetralin (5-HT$_{1A}$-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected by ${\gamma}$-mangostin. The locomotor activity stimulated by 5-FMT through the activation of at-adrenoceptors did not alter in the presence of ${\gamma}$-mangostin. 5-HT-induced inositol phosphates accumulation in mouse brain slices was abolished by ketanserin. ${\gamma}$-Mangostin caused a concentration-dependent inhibition of the inositol phosphates accumulation and the binding of [$^3H$]-spiperone, a specific 5-$HT_{2A}$ receptor antagonist, to mouse brain membranes. Kinetic analysis of the [$^H3$]-spiperone binding revealed that ${\gamma}$-mangostin increased the $_{d}$ value without affecting the $B_{max}$ value, indicating the mode of the competitive nature of the inhibition by ${\gamma}$-mangostin. These results suggest that ${\gamma}$-mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-$HT_{2A}$ receptors not by blocking the release of 5-HT from the central neurone. ${\gamma}$-Mangostin is a promising 5-$HT_{2A}$ receptors antagonist in the central nervous system.m.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.157-164
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• 1999

LB50016 was characterized as a selective and potent$ 5-HT_{1A}$ receptor agonist and evaluate it anxiolytic and antidepressant activities. It shows high affinity for $ 5-HT_{1A}$receptor, moderate affinity for $\alpha$2 adrenergic and $ 5-HT_{2A}$receptors and no significant affinity for other receptors tested. Hypothermia and increased serum corticosterone level were observed in LB50016-treated rats, which are mediated mostly by post synaptic $ 5-HT_{1A}$ receptor activation. In the mouse forced swim model for depression, LB50016-elicited dose-dependent reductions in immobility time, showing $ED_{50}$ of approximately 3 mg/kg i.p., which was blocked by pretreatment of NAN-190, $ 5-HT_{1A}$antagonist. In face-to-face test for anxiolytic activity in mice, estimated $ED_{50}$ was 2 mg/kg, i.p.. In isolation-induced aggression test with mice, fifty-fold increases in latency to attack were observed at 30 min and last up to 4 h after LB50016 treatment (3 mg/kg, i.p.). Taken together, LB50016-induced pharmacological activities are mediated by activation of $ 5-HT_{1A}$receptors, offering an effective therapeutic candidate in the management of anxiety and depression in humans.

• Toxicological Research
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• v.12 no.2
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• pp.171-179
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• 1996

To investigate the involvement of $5-HT_{2A}/ 5-HT_{2C} receptors in the developmental toxicity of cocaine in rats, mianserin (2.5 mg/kg), a $5-HT_{2A}/5-HT_{2C}$ receptor antagonist, and/or cocaine HCl (45 mg/kg) were administered intraperitoneally (i.p.), during postnatal days (PND) 7-13. Behavioral assessments for the rat pups were done after 100 days of age by using the progressive ratio schedule of reinforcement (FR 1-FR 128, doubled everyday) and cocaine challenge (5, 15 or 30 mg/kg i.p.) upon established FR 32 behavior. Cocaine injected just prior to the FR 32 session suppressed the established FR 32 responding in a dose-dependent manner. The low dose of cocaine did not affect the FR 32 responding, while the high dose of cocaine suppressed it in all experimental groups. However, by the middle dose of cocaine, rats previously received water-cocaine in their early life showed a marked resistance to cocaine-induced behavioral suppression, and this resistance was not observed in rats received both mianserin and cocaine in their early life. These results suggest that $5-HT_{2A}/ 5-HT_{2C}$ receptors may have an important role for the persistently altered behavioral sensitivity to cocaine caused by exposure to cocaine during development.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.361-367
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• 2000

Cocaine functions as indirect dopamine and serotonin (5-hydroxytryptamine, 5HT) agonists and induces genomic and behavioral alterations in the striatum. Previously we demonstrated that ritanserin, a 5HT2/1C receptor antagonist, is not responsible for cocaine-induced behavioral alterations and zif268 mRNA gene expression in the striatum (see the previous paper in this issue). In this study, it was hypothesized that dopamine and 5HT2/1C receptors are required for cocaine-induced behavioral alterations and c-fos and zif268 mRNA expression. This hypothesis was addressed by infusing amperozide which antagonizes both 5HT2/1C and dopamine receptors and was analyzed using the quantitative in situ hybridization histochemistry in vivo. Systemic injection of amperozide (5 mg/kg, s.c.) significantly blocked increase in behavior, c-fos and zif268 mRNA expression induced by 15 mg/kg cocaine, i.p., in the dorsal striatum. These data suggest that dopamine and 5HT2/1C receptors are necessary for cocaine-induced behavioral alterations and immediate early gene expression in the dorsal striatum.