5-HT1B receptors are widely distributed throughout the central nervous system with the highest concentrations found in the frontal cortex, basal ganglia, striatum, and the hippocampus.
The function of the 5-HT1B receptor differs depending upon its location. In the frontal cortex, it is believed to act as a postsynaptic receptor inhibiting the release of dopamine. In the basal ganglia and the striatum, evidence suggests 5-HT signaling acts on an autoreceptor, inhibiting the release of serotonin and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency, 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.
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.
Outside the brain, 5-HT1B receptor activation also has vascular effects, such as pulmonary vasoconstriction, which may be beneficial to the treatment of migraines.  When the 5HT1B agonist sumatriptan was first developed, one of the study participants experienced a cardiovascular event in response to intravenous administration of the drug,  so this agonist is contraindicated for patients with cardiovascular disease. 
Blocking 5-HT1B receptor signalling also increases the number of osteoblasts, bone mass, and the bone formation rate.
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. These mice have also been reported to have a lower measure of anxiety (such as on the elevated plus maze test) and a higher measure of aggression.
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 of selective serotonin reuptake inhibitor (SSRIs).[failed verification]
^Sanders AR, Cao Q, Taylor J, Levin TE, Badner JA, Cravchik A, Comeron JM, Naruya S, Del Rosario A, Salvi DA, Walczyk KA, Mowry BJ, Levinson DF, Crowe RR, Silverman JM, Gejman PV (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.
^Hudzik TJ, Yanek M, Porrey T, Evenden J, Paronis C, Mastrangelo M, Ryan C, Ross S, Stenfors C (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.
^Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR (2016). "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders". Pharmacol. Ther. 159: 1–22. doi:10.1016/j.pharmthera.2016.01.016. PMID26826604.
^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.
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, O'Dowd BF (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.
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.