Enhanced cortical extracellular levels of cholecystokinin-like material ina model of anticipation of social defeat in the rat

The involvement of cholecystokinin (CCK) in the mechanisms of stress and/or anxiety was assessed by in vivo microdialysis in rats subjected to a socia l stress paradigm. During the initial 30 min period of each conditioning se ssion, a male Sprague Dawley rat (intruder) was placed in a protective cage inside the cage of a male Tryon Maze Dull rat (resident), allowing unrestr icted visual, olfactory, and auditory contacts but precluding close physica l contact between them. During the following 15 min period, both the protec tive cage and the resident were removed (nondefeated intruders) or only the protective cage was removed allowing the resident to attack the intruder ( defeated rats). This procedure was repeated once daily for 4 d. On the fift h day, a guide cannula was implanted into the prefrontal cortex of intruder s. During a single 30 min test session, performed 4 d later, intruders were subjected to only the 30 min protected confrontation to the resident. Anxi ety-like behavior (immobility, ultrasonic vocalizations, and defensive post ures), associated with an increase (approximately +100% above baseline) in cortical outflow of CCK-like material (CCKLM), were observed in defeated in truders. Pretreatment with diazepam (5 mg/kg, i.p.), but not buspirone (0.5 -2 mg/kg, i.p.), prevented both the anxiety-related behavior and CCKLM over flow. The selective CCK-B receptor antagonist CI-988 (2 mg/kg, i.p.) reduce d the anxiety-like behavior without affecting the increase in CCKLM outflow . These data indicate that anticipation of social defeat induces a marked a ctivation of cortical CCKergic neurons associated with anxiety-related beha viors in rats.