Advance Access publication January 24, 2011 Alterations in Corticolimbic Dendritic Morphology and Emotional Behavior in Cannabinoid CB1 Receptor--Deficient Mice Parallel the Effects of Chronic Stress

Many changes produced by chronic stress are similar to those seen in cannabinoid CB1 receptor--deficient mice. In the current study, we examined both anxiety-like behavior and dendritic complexity within the prefrontal cortex and basolateral amygdala (BLA) in wild-type and CB1 receptor--deficient mice, under basal conditions and following exposure to 21 days of protracted restraint stress. CB1 receptor--deficient mice exhibited increased indices of anxiety in the elevated plus maze under basal conditions that were similar in magnitude to changes seen in wild-type mice exposed to chronic stress. Chronic stress or deletion of the CB1 receptor also produced a reduction in both apical dendritic length and branch points of neurons within layer II/III of the prelimbic region of the prefrontal cortex. Pyramidal neurons in the (BLA) of CB1 receptor--deficient mice were found to have increased dendritic length compared with wild type. Chronic stress increased dendritic length of these amygdalar neurons in both wild-type and CB1 receptor--deficient mice. Collectively, these data demonstrate that loss of cannabinoid CB1 receptor signaling produces a chronic stress-like phenotype under basal conditions and provide a putative neural substrate that may subserve the changes in emotional behavior seen following disruption of CB1 receptor signaling