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The Journal of Neuroscience, January 1, 2001, 21(1):262-269

Enhanced Cortical Extracellular Levels of Cholecystokinin-Like Material in a Model of Anticipation of Social Defeat in the Rat

Chrystel Becker¹, Marie-Hélène Thiébot¹, Yvan Touitou², Michel Hamon¹, François Cesselin^{1, 2}, and Jean-Jacques Benoliel^{1, 2}

¹ Institut National de la Santé et de la Recherche Médicale U. 288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, and ² Service de Biochimie Médicale, Faculté de Médecine Pitié-Salpêtrière, 75634 Paris Cedex 13, France

The involvement of cholecystokinin (CCK) in the mechanisms of stress and/or anxiety was assessed by in vivo microdialysis in rats subjected to a social stress paradigm. During the initial 30 min period of each conditioning session, a male Sprague Dawley rat (intruder) was placed in a protective cage inside the cage of a male Tryon Maze Dull rat (resident), allowing unrestricted visual, olfactory, and auditory contacts but precluding close physical contact between them. During the following 15 min period, both the protective 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 fifth day, a guide cannula was implanted into the prefrontal cortex of intruders. During a single 30 min test session, performed 4 d later, intruders were subjected to only the 30 min protected confrontation to the resident. Anxiety-like behavior (immobility, ultrasonic vocalizations, and defensive postures), associated with an increase (approximately +100% above baseline) in cortical outflow of CCK-like material (CCKLM), were observed in defeated intruders. 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 overflow. The selective CCK-B receptor antagonist CI-988 (2 mg/kg, i.p.) reduced the anxiety-like behavior without affecting the increase in CCKLM outflow. These data indicate that anticipation of social defeat induces a marked activation of cortical CCKergic neurons associated with anxiety-related behaviors in rats.

Key words: CCK; in vivo microdialysis; frontal cortex; anticipation of social defeat; anxiolytics; stress; anxiety

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Copyright © 2001 Society for Neuroscience  0270-6474/01/211262-08$05.00/0

This article has been cited by other articles:

				T. Gallopin, H. Geoffroy, J. Rossier, and B. Lambolez Cortical Sources of CRF, NKB, and CCK and Their Effects on Pyramidal Cells in the Neocortex Cereb Cortex, October 1, 2006; 16(10): 1440 - 1452. [Abstract] [Full Text] [PDF]

				J. Andre, B. Zeau, M. Pohl, F. Cesselin,, J.-J. Benoliel,, and C. Becker Involvement of Cholecystokininergic Systems in Anxiety-Induced Hyperalgesia in Male Rats: Behavioral and Biochemical Studies J. Neurosci., August 31, 2005; 25(35): 7896 - 7904. [Abstract] [Full Text] [PDF]

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