Hcrtr1 and 2 signaling differentially regulates depression-like behaviors

MM Scott, JN Marcus, A Pettersen, SG Birnbaum… - Behavioural brain …, 2011 - Elsevier
MM Scott, JN Marcus, A Pettersen, SG Birnbaum, T Mochizuki, TE Scammell, EJ Nestler
Behavioural brain research, 2011Elsevier
The orexin/hypocretin system has the potential to significantly modulate affect, based on
both the neuroanatomical projection patterns of these neurons and on the sites of orexin
receptor expression. However, there is little data supporting the role of specific orexin
receptors in the modulation of depression-like behavior. Here we report behavioral profiling
of mice after genetic or pharmacologic inhibition of hcrtr1 and 2 receptor signaling. Hcrtr1
null mice displayed a significant reduction in behavioral despair in the forced swim test and …
Abstract
The orexin/hypocretin system has the potential to significantly modulate affect, based on both the neuroanatomical projection patterns of these neurons and on the sites of orexin receptor expression. However, there is little data supporting the role of specific orexin receptors in the modulation of depression-like behavior. Here we report behavioral profiling of mice after genetic or pharmacologic inhibition of hcrtr1 and 2 receptor signaling. Hcrtr1 null mice displayed a significant reduction in behavioral despair in the forced swim test and tail suspension test. Wild-type mice treated with the hcrtr1 antagonist SB-334867 also displayed a similar reduction in behavioral despair. No difference in anxiety-like behavior was noted following hcrtr1 deletion. In contrast, hcrtr2-null mice displayed an increase in behavioral despair with no effect on measures of anxiety. These studies suggest that the balance of orexin action at either the hcrtr1 or the hcrtr2 receptor produces an anti-depressant or pro-depressant like effect, depending on the receptor subtype activated.
Elsevier