[7] 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.

In the basal ganglia and the striatum, evidence suggests 5-HT signaling acts on an autoreceptor, inhibiting the release of serotonin[9] and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency,[10] respectively.

In the hippocampus, a recent study has demonstrated that activation of postsynaptic 5-HT1B heteroreceptors produces a facilitation in excitatory synaptic transmission which is altered in depression.

The high distribution of vasoconstrictive 5-HT1B and 5-HT1D receptors around the brain makes them a valuable drug target for the treatment of migraines.

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).