A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression-Related Behaviors

Neuropsychopharmacology. 2016 Nov;41(12):2941-2950. doi: 10.1038/npp.2016.109. Epub 2016 Jun 29.


The effects of serotonin (5-HT) on anxiety and depression are mediated by a number of 5-HT receptors, including autoreceptors that act to inhibit 5-HT release. While the majority of anxiety and depression-related research has focused on the 5-HT1A receptor, the 5-HT1B receptor has a lesser known role in modulating emotional behavior. 5-HT1B receptors are inhibitory GPCRs located on the presynaptic terminal of both serotonin and non-serotonin neurons, where they act to inhibit neurotransmitter release. The autoreceptor population located on the axon terminals of 5-HT neurons is a difficult population to study due to their diffuse localization throughout the brain that overlaps with 5-HT1B heteroreceptors (receptors located on non-serotonergic neurons). In order to study the contribution of 5-HT1B autoreceptors to anxiety and depression-related behaviors, we developed a genetic mouse model that allows for selective ablation of 5-HT1B autoreceptors. Mice lacking 5-HT1B autoreceptors displayed the expected increases in extracellular serotonin levels in the ventral hippocampus following administration of a selective serotonin reuptake inhibitor. In behavioral studies, they displayed decreased anxiety-like behavior in the open field and antidepressant-like effects in the forced swim and sucrose preference tests. These results suggest that strategies aimed at blocking 5-HT1B autoreceptors may be useful for the treatment of anxiety and depression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Anxiety / genetics
  • Anxiety / metabolism*
  • Autoreceptors / genetics
  • Autoreceptors / metabolism*
  • Depression / genetics
  • Depression / metabolism*
  • Disease Models, Animal
  • Exploratory Behavior / physiology
  • Food Preferences / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Iodine Isotopes / pharmacokinetics
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pindolol / analogs & derivatives
  • Pindolol / pharmacokinetics
  • Receptor, Serotonin, 5-HT1B / deficiency*
  • Receptor, Serotonin, 5-HT1B / genetics
  • Receptors, Serotonin, 5-HT1 / genetics
  • Receptors, Serotonin, 5-HT1 / metabolism
  • Serotonin Antagonists / pharmacokinetics
  • Serotonin Plasma Membrane Transport Proteins / metabolism


  • Autoreceptors
  • Iodine Isotopes
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin Plasma Membrane Transport Proteins
  • cyanopindolol
  • Pindolol