Anxiety in a transgenic mouse model of cortical-limbic neuro-potentiated compulsive behavior.
Anxiety and amygdalar stimulation may induce or exacerbate compulsions triggered by cortical-limbic hyperactivity, as in human obsessive-compulsive disorder (OCD). We previously created transgenic mice that exhibit OCD-like biting, movement and behavioral perseverance abnormalities. These behaviors are caused by expression of a neuro-potentiating cholera toxin (CT) transgene in dopamine D1 receptor-expressing (D1+) neurons within the amygdalar intercalated nucleus (ICN) and within cortical areas that project to orbitofrontal cortex and striatum. Here we tested whether anxiety and increased amygdalar stimulation may play a role in eliciting or exacerbating such behaviors. D1CT mice exhibited increased thigmotaxis (tendency of mice to remain along the perimeter of open areas) in the open field assay, and increased latency to first transit and reduced transit number in the light-dark assay. These studies indicate that the D1CT mice exhibit a significant increase in behavioral indicators of anxiety. Furthermore, yohimbine, a drug that induces both amygdalar stimulation and behavioral indicators of anxiety, exacerbated abnormal leaping in D1CT mice but failed to exacerbate their abnormal behavioral perseverance. These data suggest that chronic potentiation of D1+ neurons in the amygdalar ICN increases anxiety and facilitates particular compulsive behaviors.
McGrath
M J
MJ
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
Campbell
K M
KM
Veldman
M B
MB
Burton
F H
FH
D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D003192:Compulsive Behavior / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007395:Interneurons / Q000502:physiology; D008032:Limbic System / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000503:physiopathology; D009771:Obsessive-Compulsive Disorder / Q000235:genetics / Q000503:physiopathology; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000502:physiology
D017447:Receptors, Dopamine D1