Anxiety in a transgenic mouse model of cortical-limbic neuropotentiated compulsive behavior

Anxiety and amygdalar stimulation may induce or exacerbate compulsions trig gered by cortical-limbic hyperactivity, as in human obsessive-compulsive di sorder (OCD). We previously created transgenic mice that exhibit OCD-like b iting, movement and behavioral perseverance abnormalities. These behaviors are caused by expression of a neuropotentiating cholera toxin (CT) transgen e in dopamine D1 receptor-expressing (D1+) neurons within the amygdalar int ercalated nucleus (ICN) and within cortical areas that project to orbitofro ntal cortex and striatum. Here we tested whether anxiety and increased amyg dalar stimulation may play a role in eliciting or exacerbating such behavio rs. D1CT mice exhibited increased thigmotaxis (tendency of mite to remain a long the perimeter of open areas) in the open field assay, and increased la tency 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 indu ces both amygdalar stimulation and behavioral indicators of anxiety, exacer bated abnormal leaping in D1CT mice but failed to exacerbate their abnormal behavioral perseverance. These data suggest that chronic potentiation of D 1+ neurons in the amygdalar ICN increases anxiety and facilitates particula r compulsive behaviors. (C) 1999 Lippincott Williams & Wilkins.