5-HT7 receptor inhibition and inactivation induce antidepressantlike behavior and sleep pattern

Biol Psychiatry. 2005 Nov 15;58(10):831-7. doi: 10.1016/j.biopsych.2005.05.012. Epub 2005 Jul 14.

Abstract

Background: The 5-hydroxytryptamine7 receptor (5-HT7) is implicated in circadian rhythm phase resetting, and 5-HT7 receptor-selective antagonists alter rapid eye movement (REM) sleep parameters in a pattern opposite from those in patients with clinical depression.

Methods: As sleep, circadian rhythm, and mood regulation are related, we examined 5-HT7 receptor knockout mice in two behavioral models of depression. The forced swim and tail suspension tests are highly predictive for antidepressant drug activity.

Results: Unmedicated 5-HT7-/- mice showed decreased immobility in both tests, consistent with an antidepressantlike behavior. The selective 5-HT7 receptor antagonist SB-269970 also decreased immobility. The selective serotonin reuptake inhibitor citalopram, a widely used antidepressant, decreased immobility in both 5-HT7+/+ and 5-HT7-/- mice in the tail suspension test, suggesting that it utilizes an independent mechanism. The 5-HT7-/- mice spent less time in and had less frequent episodes of REM sleep, also consistent with an antidepressantlike state.

Conclusions: The 5-HT7 receptor might have a role in mood disorders and antagonists might have therapeutic value as antidepressants.

Publication types

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

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology
  • Depressive Disorder / physiopathology
  • Disease Models, Animal
  • Immobility Response, Tonic / drug effects
  • Immobility Response, Tonic / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenols / pharmacology*
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / physiology*
  • Sleep / physiology*
  • Sleep, REM / drug effects
  • Sulfonamides / pharmacology*

Substances

  • Antidepressive Agents
  • Phenols
  • Receptors, Serotonin
  • SB 269970
  • Sulfonamides
  • serotonin 7 receptor