5-HT7 receptor inhibition and inactivation induce antidepressantlike behavior and sleep pattern.
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.
Hedlund
Peter B
PB
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Huitron-Resendiz
Salvador
S
Henriksen
Steven J
SJ
Sutcliffe
J Gregor
JG
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D003866:Depressive Disorder / Q000503:physiopathology; D004195:Disease Models, Animal; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010636:Phenols / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*
D000928:Antidepressive Agents; D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D013449:Sulfonamides; C104425:serotonin 7 receptor