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Pharmacology, Biochemistry, and Behavior Oct 2021Serotonin (5-HT) is known to play a critical role in regulation of essential neural processes, whereas more recent research highlights serotonin's modulatory effects on... (Review)
Review
Serotonin (5-HT) is known to play a critical role in regulation of essential neural processes, whereas more recent research highlights serotonin's modulatory effects on cognition and executive functioning. Current examinations have identified specific serotonin receptors for their direct impact on behavioral flexibility. Providing definitive evidence for the impact of specific receptor targets on behavioral flexibility is difficult, due to the range of behavioral tests used. Due to limited studies and the sheer amount of different serotonin receptor targets, beginning to bring these studies together is important for the field. Our current review of the literature aims to differentiate how modulation of specific 5-HT receptors affects behavioral flexibility. Although more studies have examined 5-HT, 5-HT, and 5-HT receptors, it is unclear why this is the case. Above all, there are some paradoxical results pertaining to these receptor targets. There is a clear distinction between 5-HT and 5-HT, which conveys that these two receptor subtypes have inverse effects when compared to each other. In addition, some findings support one another, such as upregulation of 5-HT receptors impairs flexibility, while blockade alleviates this impairment in both drug-induced and disease model rodent studies. Further understanding how modulatory effects of specific 5-HT receptors impact behavioral flexibility is imperative to advance the development of new therapeutics for neuropsychiatric disorders afflicted by behavioral inflexibility.
Topics: Animals; Behavior, Animal; Cognition; Executive Function; Female; Humans; Male; Mice; Rats; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Reversal Learning; Serotonin
PubMed: 34314738
DOI: 10.1016/j.pbb.2021.173243 -
Pharmacology & Therapeutics Jun 2015Serotonin receptors are prevalent throughout the nervous system and the periphery, and remain one of the most lucrative and promising drug discovery targets for... (Review)
Review
Serotonin receptors are prevalent throughout the nervous system and the periphery, and remain one of the most lucrative and promising drug discovery targets for disorders ranging from migraine headaches to neuropsychiatric disorders such as schizophrenia and depression. There are 14 distinct serotonin receptors, of which 13 are G protein-coupled receptors (GPCRs), which are targets for approximately 40% of the approved medicines. Recent crystallographic and biochemical evidence has provided a converging understanding of the basic structure and functional mechanics of GPCR activation. Currently, two GPCR crystal structures exist for the serotonin family, the 5-HT1B and 5-HT2B receptor, with the antimigraine and valvulopathic drug ergotamine bound. The first serotonin crystal structures not only provide the first evidence of serotonin receptor topography but also provide mechanistic explanations into functional selectivity or biased agonism. This review will detail the findings of these crystal structures from a molecular and mutagenesis perspective for driving rational drug design for novel therapeutics incorporating biased signaling.
Topics: Allosteric Site; Animals; Ergotamine; GTP-Binding Proteins; Heart Valve Diseases; Humans; Migraine Disorders; Models, Molecular; Protein Conformation; Receptor, Serotonin, 5-HT1B; Receptor, Serotonin, 5-HT2B; Receptors, Serotonin; Serotonin Receptor Agonists; Signal Transduction; Vasoconstrictor Agents
PubMed: 25601315
DOI: 10.1016/j.pharmthera.2015.01.009 -
Psychopharmacology Series 1993
Review
Topics: Animals; Humans; Kinetics; Receptors, Serotonin
PubMed: 8361973
DOI: 10.1007/978-3-642-78010-3_3 -
The Journal of Clinical Psychiatry 1996The demonstrated efficacy in anxiety disorders of drugs such as buspirone or fluoxetine has emphasized the importance of 5-hydroxytryptamine (5-HT or serotonin).... (Review)
Review
The demonstrated efficacy in anxiety disorders of drugs such as buspirone or fluoxetine has emphasized the importance of 5-hydroxytryptamine (5-HT or serotonin). Buspirone is a selective agonist at a subtype of serotonin receptor termed 5-HT1A, whereas fluoxetine is a selective inhibitor of the reuptake of 5-HT. At least 14 types of mammalian serotonin receptors have been isolated and classified into seven major families, using pharmacologic, transductional, and structural criteria. The subtypes of serotonin receptors are localized in different regions of the brain. Selective compounds for particular subtypes of serotonin receptors may yield selective pharmacologic effects. Since the latency between the initiation of treatment with an SSRI and the appearance of clinical effects may be due to the desensitization of presynaptic autoreceptors, the development of drugs to decrease latency is an active area of investigation. This article provides a brief overview of the physiology and pharmacology of serotonin systems so that the relationship between serotonin compounds and anxiety can be better understood.
Topics: Anxiety Disorders; Buspirone; Fluoxetine; Humans; Receptors, Serotonin; Selective Serotonin Reuptake Inhibitors
PubMed: 8647798
DOI: No ID Found -
Digestive Diseases and Sciences Aug 1999Several serotonin (5-HT) receptor subtypes have been defined by pharmacological responses to selective agonists and antagonists and by pathways of receptor-effector... (Review)
Review
Several serotonin (5-HT) receptor subtypes have been defined by pharmacological responses to selective agonists and antagonists and by pathways of receptor-effector coupling. Using molecular techniques, additional receptor subtypes have been described. 5-HT receptors are prevalent in the central nervous system and gut and participate in induction of emesis. 5-HT3 antagonists are used to prevent emesis from cancer chemotherapy and also demonstrate efficacy in radiation-induced nausea, postoperative nausea, hyperemesis gravidarum, and nausea and vomiting with the acquired immunodeficiency syndrome. 5-HT4 agonists exhibit prokinetic properties in nauseated patients with gastroparesis and functional dyspepsia. Conversely, 5-HT4 antagonists have antiemetic activity in some experimental models. The 5-HT1D receptor agonist sumatriptan reduces emesis with migraine headaches and in cyclic vomiting syndrome, most likely via action on central nervous system sites. In other models, 5-HT1A and 5-HT2A/5-HT2C agonists exhibit antiemetic properties. The utility of 5-HT receptor ligands in treating emesis is the subject of active investigation.
Topics: Adolescent; Adult; Central Nervous System; Child; Child, Preschool; Enteric Nervous System; Female; Humans; Infant; Male; Periodicity; Receptors, Serotonin; Serotonin Agents; Syndrome; Vomiting
PubMed: 10490049
DOI: No ID Found -
Journal of Cell Science Aug 2019Protein-protein interaction is often investigated using quantitative molecular microscopy with Förster resonant energy transfer (FRET). Here, we combined 'linear...
Protein-protein interaction is often investigated using quantitative molecular microscopy with Förster resonant energy transfer (FRET). Here, we combined 'linear unmixing FRET' (lux-FRET) with the simultaneous application of a FRET-based biosensor for cAMP to investigate the oligomerization between the 5-HT receptor (5-HTR, also known as HTR7) and the 5-HT receptor (5-HTR, also known as HTR1A) and its importance for cAMP signaling. We found that the 5-HTR not only stimulates cAMP production, but also forms hetero-oligomers with 5-HTR, which blocks the inhibitory effect of the latter. 5-HTR signaling, however, is not affected by this hetero-oligomerization. By modeling the kinetics of intracellular cAMP level changes in relation to the 5-HTR:5-HTR stoichiometry, we were able to decipher the complex signaling characteristics of endogenous serotonin receptors in cultured hippocampal neurons. Our findings indicate that serotonergic signaling is not only modulated by the concentration of an individual receptor but also by its specific interaction with other receptors in endogenous systems. We conclude that the regulated ratio of serotonin receptors in immature and mature neurons may be critically involved in both the onset and response to treatments of psychiatric diseases, such as anxiety and depression.
Topics: Animals; Cell Line, Tumor; Cyclic AMP; Mice; Protein Multimerization; Receptor, Serotonin, 5-HT1A; Receptors, Serotonin; Second Messenger Systems
PubMed: 31371490
DOI: 10.1242/jcs.230334 -
Progress in Brain Research 1988
Review
Topics: Animals; Pain; Receptors, Serotonin; Spinal Cord
PubMed: 3064176
DOI: 10.1016/s0079-6123(08)62801-0 -
Annals of the New York Academy of... 1990
Review
Topics: Animals; Brain; Kinetics; Receptors, Serotonin
PubMed: 2252304
DOI: 10.1111/j.1749-6632.1990.tb16876.x -
Critical Reviews in Neurobiology 1994The field of serotonin (5HT) receptor pharmacology has been at least as dramatically altered by the advent of molecular neurobiology and recombinant DNA techniques as... (Review)
Review
The field of serotonin (5HT) receptor pharmacology has been at least as dramatically altered by the advent of molecular neurobiology and recombinant DNA techniques as has any other neurotransmitter receptor field. The principal reason for this is the unforeseen multitude of genes expressing different types of 5HT receptors. Classic pharmacological studies as well as radioligand binding studies convinced workers in the field that there were multiple 5HT receptors. The extent of that multiplicity was not generally foreseen. At the time of this writing, no less than 13 5HT receptor genes have been cloned and functionally expressed. In addition, a fourteenth receptor has been well studied and will undoubtedly be cloned in the near future. These novel 5HT receptor clones are appearing at an astonishing rate. All 13 receptors have been cloned between the years 1987 to 1993, with more than half of the clones appearing in the literature in the last 18 months. Furthermore, there is no indication that all of the 5HT receptors present in the mammalian genome have been cloned. In fact, there are classic pharmacological data as well as radioligand binding data that implicate the existence of additional 5HT receptor subtypes not yet fully defined or cloned. Bringing order to this rapid outpouring of information at this time is a very difficult task. Not only is there a great multiplicity of receptor subtypes, each with a unique pharmacology and distribution, but there are species variants of 5HT receptors. In order to provide a concise and timely review, this article focuses on the strategies used to clone and express multiple 5HT receptors. Unique properties of the various receptors are emphasized.
Topics: Amino Acid Sequence; Animals; Cloning, Molecular; Humans; Molecular Sequence Data; Receptors, Serotonin
PubMed: 7923395
DOI: No ID Found -
The British Journal of Psychiatry.... Sep 1991Serotonin (5-HT) interacts with multiple brain 5-HT receptor subtypes to influence a wide range of behaviours. Three main families of 5-HT receptors (5-HT1, 5-HT2 and... (Review)
Review
Serotonin (5-HT) interacts with multiple brain 5-HT receptor subtypes to influence a wide range of behaviours. Three main families of 5-HT receptors (5-HT1, 5-HT2 and 5-HT3) have been described which differ in their binding affinity for selective ligands, their receptor-effector coupling mechanisms, and the behavioural processes they regulate. Nevertheless, manipulation of several different 5-HT receptor subtypes (5-HT1A, 5-HT1C, 5-HT2 and 5-HT3) may produce anxiolytic effects; 5-HT1A and 5-HT2 receptors may be involved in the aetiology of major depression and the therapeutic effects of antidepressant treatment; and 5-HT3 receptors have been linked to reward mechanisms and cognitive processes. These advances offer therapeutic possibilities, the value of which can only be satisfactorily assessed by controlled clinical trials.
Topics: Animals; Anxiety Disorders; Arousal; Brain; Humans; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Terminology as Topic
PubMed: 1840764
DOI: No ID Found