TY - JOUR
T1 - Post-traumatic stress behavioural responses in inbred mouse strains
T2 - Can genetic predisposition explain phenotypic vulnerability?
AU - Cohen, Hagit
AU - Geva, Amir B.
AU - Matar, Michael A.
AU - Zohar, Joseph
AU - Kaplan, Zeev
PY - 2008/5/1
Y1 - 2008/5/1
N2 - Clinical studies of twin pairs and families of post-traumatic stress disorder (PTSD) patients raise questions as to possible genetic predisposition to PTSD. Studies using isogenic animal populations exposed to a stress paradigm could elucidate the relative contributions of genotype and environment to endophenotypic expression. The prevalence of individuals displaying severely compromised behavioural responses to predator scent stress (PSS) was assessed in six inbred strains of mice in an animal model of PTSD that classifies individuals into groups according to the degree of their behavioural response. The choice of strains was based on the frequent use of these mice in transgenic research. The prevalence of extreme behavioural response in the elevated plus maze and the acoustic startle response paradigms, performed in sequence, was assessed at baseline and 7 d after PSS exposure between and within strains, and compared to differences in circulating corticosterone levels. Narrow-sense trait heritability was determined by comparing the between-strain variance to the total variance. Although strain-specific differences in anxiety-like behaviours were demonstrated, the results revealed a significant degree of individual variability in response patterns within each of the inbred strains, yielding a baseline heritability factor for anxiety-like behaviours of 30%, but only 10% for response to stress exposure. Baseline anxiety-like behaviours were found not to be predictive of post-exposure behavioural responses. The response of the individual to stress is multifactorial and environmental factors play a predominant role in characterizing the individual response to stress exposure, although there are significant genetic underpinnings.
AB - Clinical studies of twin pairs and families of post-traumatic stress disorder (PTSD) patients raise questions as to possible genetic predisposition to PTSD. Studies using isogenic animal populations exposed to a stress paradigm could elucidate the relative contributions of genotype and environment to endophenotypic expression. The prevalence of individuals displaying severely compromised behavioural responses to predator scent stress (PSS) was assessed in six inbred strains of mice in an animal model of PTSD that classifies individuals into groups according to the degree of their behavioural response. The choice of strains was based on the frequent use of these mice in transgenic research. The prevalence of extreme behavioural response in the elevated plus maze and the acoustic startle response paradigms, performed in sequence, was assessed at baseline and 7 d after PSS exposure between and within strains, and compared to differences in circulating corticosterone levels. Narrow-sense trait heritability was determined by comparing the between-strain variance to the total variance. Although strain-specific differences in anxiety-like behaviours were demonstrated, the results revealed a significant degree of individual variability in response patterns within each of the inbred strains, yielding a baseline heritability factor for anxiety-like behaviours of 30%, but only 10% for response to stress exposure. Baseline anxiety-like behaviours were found not to be predictive of post-exposure behavioural responses. The response of the individual to stress is multifactorial and environmental factors play a predominant role in characterizing the individual response to stress exposure, although there are significant genetic underpinnings.
KW - Animal model
KW - Corticosterone
KW - Environmental factor
KW - Extreme behavioural response
KW - Genetic factor
KW - Heritability
KW - Inbred strains
KW - Minimal behavioural response
KW - Post-traumatic stress disorder
UR - http://www.scopus.com/inward/record.url?scp=41649109189&partnerID=8YFLogxK
U2 - 10.1017/S1461145707007912
DO - 10.1017/S1461145707007912
M3 - Article
C2 - 17655807
AN - SCOPUS:41649109189
VL - 11
SP - 331
EP - 349
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
SN - 1461-1457
IS - 3
ER -