Regulation of dorsal raphe nucleus function by serotonin autoreceptors: a behavioral perspective

J Chem Neuroanat. 2011 Jul;41(4):234-46. doi: 10.1016/j.jchemneu.2011.05.001. Epub 2011 May 8.

Abstract

Neurotransmission by serotonin (5-HT) is tightly regulated by several autoreceptors that fine-tune serotonergic neurotransmission through negative feedback inhibition at the cell bodies (predominantly 5-HT(1A)) or at the axon terminals (predominantly 5-HT(1B)); however, more subtle roles for 5-HT(1D) and 5-HT(2B) autoreceptors have also been detected. This review provides an overview of 5-HT autoreceptors, focusing on their contribution in animal behavioral models of stress and emotion. Experiments targeting 5-HT autoreceptors in awake, behaving animals have generally shown that increasing autoreceptor feedback is anxiolytic and rewarding, while enhanced 5-HT function is aversive and anxiogenic; however, the role of serotonergic activity in behavioral models of helplessness is more complex. The prevailing model suggests that 5-HT autoreceptors become desensitized in response to stress exposure and antidepressant administration, two seemingly opposite manipulations. Thus there are still unresolved questions regarding the role of these receptors-and serotonin in general-in normal and pathological states.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoreceptors / metabolism*
  • Emotions
  • Humans
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Neurons / cytology
  • Neurons / metabolism*
  • Presynaptic Terminals / metabolism
  • Raphe Nuclei / metabolism*
  • Rats
  • Receptor, Serotonin, 5-HT2B / genetics
  • Receptor, Serotonin, 5-HT2B / metabolism*
  • Receptors, Serotonin, 5-HT1 / genetics
  • Receptors, Serotonin, 5-HT1 / metabolism*
  • Serotonin / metabolism*
  • Stress, Physiological
  • Synaptic Transmission / physiology

Substances

  • Autoreceptors
  • Receptor, Serotonin, 5-HT2B
  • Receptors, Serotonin, 5-HT1
  • Serotonin