5-hydroxytryptamine receptor 1B also known as the5-HT1B receptor is aprotein that in humans is encoded by theHTR1Bgene.[5][6] The 5-HT1B receptor is a5-HT receptor subtype.[7]
5-HT1B receptors are widely distributed throughout thecentral nervous system with the highest concentrations found in thefrontal cortex,basal ganglia,striatum, and thehippocampus.[8]The function of the 5-HT1B receptor differs depending upon its location. In the frontal cortex, it is believed to act as a terminal receptor inhibiting the release ofdopamine. In the basal ganglia and the striatum, evidence suggests 5-HT signaling acts on anautoreceptor, inhibiting the release ofserotonin[9] and decreasing glutamatergic transmission by reducing miniatureexcitatory postsynaptic potential (mEPSP) frequency,[10] respectively. In the hippocampus, a recent study has demonstrated that activation of postsynaptic 5-HT1Bheteroreceptors produces a facilitation in excitatory synaptic transmission which is altered in depression.[11]When the expression of 5-HT1B in human cortex was traced throughout life, significant changes during adolescence were observed, in a way that is strongly correlated with the expression of 5-HT1E.[12]
Outside of the CNS, the 5-HT1B receptor is also expressed on theendothelium of blood vessels, particularly in themeninges.[13] Activation of these receptors results invasoconstriction. The high distribution of vasoconstrictive 5-HT1B and5-HT1D receptors around the brain makes them a valuable drug target for the treatment of migraines.[13]
Blocking 5-HT1B receptor signalling also increases the number ofosteoblasts, bone mass, and the bone formation rate.[14]
Knockout mice lacking the 5-HT1B gene have been reported to have a higher preference for alcohol, although later studies failed to replicate such abnormalities in alcohol consumption.[15] These mice have also been reported to have a lower measure of anxiety (such as on theelevated plus maze test) and a higher measure of aggression.[15]
Under basal conditions, knockout mice present with a "normal" phenotype and exhibit a sucrose preference (lack of sucrose preference is considered a measure of anhedonia). However, after undergoing chronic unpredictable stress treatment to induce a "depression-like" phenotype these animals do not benefit from administration ofselective serotonin reuptake inhibitor (SSRIs).[11][failed verification]
^Sanders AR, Cao Q, Taylor J, Levin TE, Badner JA, Cravchik A, et al. (Feb 2001). "Genetic diversity of the human serotonin receptor 1B (HTR1B) gene".Genomics.72 (1):1–14.doi:10.1006/geno.2000.6411.PMID11247661.
^Shoval G, Bar-Shira O, Zalsman G, John Mann J, Chechik G (Jul 2014). "Transitions in the transcriptome of the serotonergic and dopaminergic systems in the human brain during adolescence".European Neuropsychopharmacology.24 (7):1123–32.doi:10.1016/j.euroneuro.2014.02.009.PMID24721318.S2CID14534307.
^Martinez-Price D, Krebs-Thomson K, Geyer M (1 January 2002). "Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies".Addiction Research & Theory.10 (1). Informa UK Limited:43–67.doi:10.1080/16066350290001704.ISSN1606-6359.
^Rempel NL, Callaway CW, Geyer MA (May 1993). "Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release".Neuropsychopharmacology.8 (3):201–211.doi:10.1038/npp.1993.22.PMID8099482.
^Scearce-Levie K, Viswanathan SS, Hen R (January 1999). "Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT1B receptor".Psychopharmacology.141 (2). Berlin:154–161.doi:10.1007/s002130050819.PMID9952039.
^abcWO 2022/010937, Baggott M, "Advantageous benzothiophene compositions for mental disorders or enhancement.", published 13 January 2022, assigned to Tactogen Inc.
^Hudzik TJ, Yanek M, Porrey T, Evenden J, Paronis C, Mastrangelo M, et al. (Mar 2003). "Behavioral pharmacology of AR-A000002, a novel, selective 5-hydroxytryptamine(1B) antagonist".The Journal of Pharmacology and Experimental Therapeutics.304 (3):1072–84.doi:10.1124/jpet.102.045468.PMID12604684.S2CID20463714.
^Tsai SJ, Wang YC, Chen JY, Hong CJ (2003). "Allelic variants of the tryptophan hydroxylase (A218C) and serotonin 1B receptor (A-161T) and personality traits".Neuropsychobiology.48 (2):68–71.doi:10.1159/000072879.PMID14504413.S2CID42559772.
Olivier B, van Oorschot R (Dec 2005). "5-HT1B receptors and aggression: a review".European Journal of Pharmacology.526 (1–3):207–17.doi:10.1016/j.ejphar.2005.09.066.PMID16310769.
Hamblin MW, Metcalf MA, McGuffin RW, Karpells S (Apr 1992). "Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with 5-HT1D-like pharmacological specificity".Biochemical and Biophysical Research Communications.184 (2):752–9.doi:10.1016/0006-291X(92)90654-4.PMID1315531.
Veldman SA, Bienkowski MJ (Sep 1992). "Cloning and pharmacological characterization of a novel human 5-hydroxytryptamine1D receptor subtype".Molecular Pharmacology.42 (3):439–44.PMID1328844.
Mochizuki D, Yuyama Y, Tsujita R, Komaki H, Sagai H (Jun 1992). "Cloning and expression of the human 5-HT1B-type receptor gene".Biochemical and Biophysical Research Communications.185 (2):517–23.doi:10.1016/0006-291X(92)91655-A.PMID1610347.
Nöthen MM, Erdmann J, Shimron-Abarbanell D, Propping P (Dec 1994). "Identification of genetic variation in the human serotonin 1D beta receptor gene".Biochemical and Biophysical Research Communications.205 (2):1194–200.doi:10.1006/bbrc.1994.2792.PMID7802650.
Ng GY, George SR, Zastawny RL, Caron M, Bouvier M, Dennis M, et al. (Nov 1993). "Human serotonin1B receptor expression in Sf9 cells: phosphorylation, palmitoylation, and adenylyl cyclase inhibition".Biochemistry.32 (43):11727–33.doi:10.1021/bi00094a032.PMID8218242.
Bouchelet I, Cohen Z, Case B, Séguéla P, Hamel E (Aug 1996). "Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels".Molecular Pharmacology.50 (2):219–23.PMID8700126.
Varnäs K, Hall H, Bonaventure P, Sedvall G (Oct 2001). "Autoradiographic mapping of 5-HT(1B) and 5-HT(1D) receptors in the post mortem human brain using [(3)H]GR 125743".Brain Research.915 (1):47–57.doi:10.1016/S0006-8993(01)02823-2.PMID11578619.S2CID43104381.
Hasegawa Y, Higuchi S, Matsushita S, Miyaoka H (Apr 2002). "Association of a polymorphism of the serotonin 1B receptor gene and alcohol dependence with inactive aldehyde dehydrogenase-2".Journal of Neural Transmission.109 (4):513–21.doi:10.1007/s007020200042.PMID11956970.S2CID35750034.
Sinha R, Cloninger CR, Parsian A (Aug 2003). "Linkage disequilibrium and haplotype analysis between serotonin receptor 1B gene variations and subtypes of alcoholism".American Journal of Medical Genetics Part B.121B (1):83–8.doi:10.1002/ajmg.b.20064.PMID12898580.S2CID33460360.
