Changes in brain cholecystokinin and anxiety-like behavior following exposure of mice to predator odor

Exposure of CD-1 mice to a familiar environment lined with clean shavings (control odor) as well as a familiar environment lined with soiled rat shavings (predator odor) induced anxiety in the light/dark box. Mice exposed to the familiar environment or predator odor displayed decreased latency to enter the dark chamber of the light/dark box and spent less time in the light portion of the apparatus relative to home-caged mice. Mice exposed to the familiar environment lined with clean shavings or predator odor displayed elevated cholecystokinin mRNA levels from the ventral tegmental area, medial and basolateral nuclei of the amygdala relative to home-caged mice. Exposure of CD-1 mice to 2, 5 or 10 min of predator odor increased acoustic startle relative to mice merely exposed to the familiar environment lined with clean shavings at protracted intervals. Mice exposed to the familiar environment lined with clean shavings did not exhibit enhanced startle relative to home-caged mice. Exaggerated startle reactivity was in evidence immediately, 24, and 48 h following a 5-min exposure of mice to predator odor. In contrast, a 10-min exposure of mice to predator odor produced an oscillating pattern of enhanced startle evident during the immediate and 48-h post-stressor intervals only. However, when the startle stimulus was withheld 1 h following odor presentation, mice exhibited enhanced startle patterns reminiscent of the 5-min exposure. The 2-min exposure of mice to predator odor produced a delayed onset of enhanced startle observed at the 168-h test interval only. Potential anxiogenic influences of mesocorticolimbic cholecystokinin availability as well as the time course and underlying neuronal substrates of long-term behavioral disturbances as a result of psychogenic stressor manipulations are discussed.