Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter-deficient mice

Biol Psychiatry. 2003 Nov 15;54(10):960-71. doi: 10.1016/s0006-3223(03)00696-6.


Background: As a key regulator of serotonergic activity and target of many antidepressant treatments, the serotonin transporter (SERT) represents a potential mediator of anxiety- and depression-related behaviors. Using mice lacking the SERT (SERT KO), we examined the role of SERT function in anxiety- and depression-related behaviors and serotonergic neuron function.

Methods: Serotonin transporter knockout mice were evaluated in paradigms designed to assess anxiety-, depression-, and stress-related behaviors. Dorsal raphe nucleus (DRN) function was assessed by quantitative serotonergic cell counting and extracellular electrical recording of neuronal firing properties.

Results: Serotonin transporter knockout mice showed an increase in latency to feed in a novel situation, more immobility in a forced swim, increased escape latency in a shock escape paradigm, and decreased immobility in tail suspension. No differences in anxiety-related behaviors were seen in the open field and the elevated plus maze. Serotonin transporter knockout mice exhibit a 50% reduction in serotonergic cell number and a fourfold decrease in firing rate in the DRN.

Conclusions: Developmental loss of SERT produces altered behaviors in models of depression that are generally opposite to those produced by antidepressant treatment. The reduced serotonergic cell number and firing rate in the DRN of adult SERT KO mice suggest a mechanism for these altered behaviors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials
  • Analgesia
  • Animals
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Autoradiography
  • Avoidance Learning
  • Behavior, Animal
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Count
  • Depression / metabolism
  • Depression / physiopathology*
  • Dose-Response Relationship, Radiation
  • Electrophysiology / methods
  • Electroshock / methods
  • Escape Reaction
  • Exploratory Behavior
  • Feeding Behavior
  • Female
  • Hindlimb Suspension
  • Immunohistochemistry
  • Iodine Isotopes / pharmacokinetics
  • Male
  • Maleates / pharmacokinetics
  • Maze Learning
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins*
  • Raphe Nuclei / metabolism
  • Raphe Nuclei / physiopathology*
  • Reaction Time
  • Serotonin Plasma Membrane Transport Proteins
  • Stress, Physiological / metabolism
  • Stress, Physiological / physiopathology
  • Swimming
  • Time Factors


  • Carrier Proteins
  • Iodine Isotopes
  • Maleates
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • dansylaminomethylmaleic anhydride