Differential effects of infralimbic vs. ventromedial orbital PFC lidocaine infusions in CD-1 mice on defensive responding in the mouse defense test battery and rat exposure test

Abstract

The ventromedial prefrontal cortex (vmPFC) is extremely sensitive to a variety of stressful situations and threatening events, and has been suggested to be an associative cortical brain system processing the integration of anxiety-related cognitive, affective and motivated behavior in rodents, primates and humans. In addition, recent evidence suggests that (a) anxiety-related affective processing appears to be lateralized to the right hemisphere vmPFC; and (b) there appears to be functional heterogeneity within the rodent vmPFC. The present study evaluated the possibility that distinct sub-areas of the right hemisphere ventral PFC might differentially influence anxiety-like defensive responding in two different predator stress situations following transient inactivation of the ventromedial orbital (vMO) or infralimbic (IL) vmPFC in CD-1 mice. In week 1, IL vmPFC lidocaine infusions reduced anxiety-like defensive responding in mice (enhanced approach and contact) confronted with a hand-held anesthetized rat stimulus in the mouse defense test battery (vMO inactivation exerted minimal effects). In week 2, vMO lidocaine infusions enhanced anxiety-like defensive responding (enhanced avoidance and protected risk assessment) toward a barricaded live rat in the rat exposure test (IL inactivation exerted minimal effects). Although it is unclear whether week 1 mouse defense test battery testing influenced week 2 rat exposure test results, these preliminary data suggest functional differences within the mouse right hemisphere ventral PFC related to cautious evaluation of predator threat. Given the dense unilateral reciprocal connectivity between the IL and vMO subregions of the PFC, both associative ventromedial cortical areas may exert complimentary yet dissociable roles in the processing of threat stimuli. This suggests that while the IL vmPFC may mediate cautious evaluation of threat situations (risk assessment), the vMO PFC may inhibit prepotent avoidance responses to facilitate such IL-mediated adaptive behavioral responses.