The International Journal of Neuropsychopharmacology

Research Article

Exposure to extreme stress impairs contextual odour discrimination in an animal model of PTSD

Hagit Cohena1 c1, Israel Liberzona2 and Gal Richter-Levina3

a1 Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

a2 Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA

a3 Department of Psychology, University of Haifa, Israel

Abstract

Post-traumatic stress disorder (PTSD) patients respond to trauma-related danger cues even in objectively safe environments as if they were in the original event, seemingly unable to adequately modulate their responses based on the contextual cues present. In order to model this inability to utilize contextualized memory, in an animal model of PTSD, a novel experimental paradigm of contextual cue processing was developed – the differential contextual odour conditioning (DCOC) paradigm – and tested in trauma-exposed animals and controls. In the DCOC paradigm, animals encountered cinnamon odour in both an aversive environment and a rewarding (safe) environment. Response (freezing) to cinnamon odour was tested in a third, neutral environment to examine the ability of animals to modulate their responses based on the contextual cues. The effect of exposure to traumatic stressors, e.g. predator scent stress (PSS) and underwater trauma (UWT), on contextual cue discrimination was assessed. Rats trained in the DCOC paradigm acquired the ability to modulate their behavioural responses to odour cue based on contextual cues signalling safe vs. dangerous environment. The PSS and UWT stressors abolished the ability to modulate their responses based on contextual cues, both when exposure preceded DCOC training, and when it followed successfully completed training. The DCOC paradigm offers a promising model for studying the neurobiological basis of contextual modulation of response to potential threat in animals, a process that is disrupted by exposure to severe stress/trauma, and thus might be particularly salient for the study of PTSD.

(Received April 17 2008)

(Reviewed May 12 2008)

(Revised June 17 2008)

(Accepted June 27 2008)

(Online publication August 13 2008)

Correspondence:

c1 Address for correspondence: H. Cohen, Ph.D. Anxiety and Stress Research Unit, Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 4600, Beer-Sheva 84170, Israel. Tel.: 972-8-6401743 Fax: 972-8-6401742 E-mail: hagitc@bgu.ac.il.