he influence of genetic factors on
the nature andintensity of stress responses has been widely demon-strated in several animal species1 and
in humans.2 Thisgenetic component may be directly responsible
for thelarge interindividual variation often
observed for this kindof trait, or, as indicated
by recent findings, it may provokevariations through interaction between
genotype andenvironment, including postnatal
environment.3 The useof intraspecific groups of animals that differ in theirgenetic backgrounds and/or their responses
to environ-mental challenges has gained more
and more interest.Theselection of divergent rat or mouse
strains that differ intheir behavioral responses to well-defined
stressors, such3 6 8B a s i c r e s e a r c hThere is much evidence for the involvement
of central monoaminergic systems, the key targets of stress, in the regula-tion of mood. Animal and human findings
indicate that genetics play a role in the etiology of mood disorders, and so
weselected divergent inbred rat strains
according to their anxiety-related behaviors on exposure to novel environments.
Wecompared these strains for psychoneuroendocrine
response to stressors and/or antidepressants. Molecular genetic stud-ies were also performed to localize
the genomic regions associated with these strain-dependent anxiety profiles.
We thenexamined human results indicating
that allelic variations in the serotonin transporter (5-HTT) may play a role
in the eti-ology of neuroticism and depression.
Thus, we compared inbred rat strains for the 5-HTT, with regard to central andperipheral (platelet) protein expression
and function, and the consequences of local application of a selective serotoninreuptake inhibitor (SSRI) on extracellular
serotonin (5-HT) levels. Our results indicate that spontaneously hypertensiverats and Lewis rats (LEW) selectively
diverge in terms of anxiety-related behaviors and that this divergence is located
onchromosome 4. The use of social defeat
in LEW and the analysis of its psychoneuroendocrine consequences strongly sug-gest that such a paradigm, which is
sensitive to repeated SSRI treatment, models posttraumatic stress disorder. The
Wistar-Kyoto rat may be an adequate model
to study the consequences of a genetically driven hypersensitivity to stress
andnoradrenergic antidepressants. Our
most recent findings show that the Fischer 344 and LEW strains differ in proteinexpression and function of hippocampal
and platelet 5-HTT; the divergence in protein expression is not due to allelic
vari-ations in the gene-coding sequences
and leads to marked differences in extracellular 5-HT levels under basal conditionsor SSRI. These examples illustrate
how the use of inbred rat strains may complement our knowledge on the genetics
ofbehavior, in the same way as the use
of transgenic mice.Dialogues Clin Neurosci.
2002;4:368-376.Neurogenetics of emotional reactivity to stress in animalsFrancis Chaouloff, PhDKeywords: antidepressant;
anxiety; hypothalamo-pituitary-adrenal axis; inbred ratstrain;
serotonin; serotonin transporter
and receptor; stressAuthor affiliations: :
Neurogénétique
et Stress, INSERM U471-INRA, Institut F. Magendie, Bordeaux,
FranceAddress for correspondence: Neurogénétique et Stress, INSERM U471-INRA, Institut F. Magendie, Rue Camille Saint Saëns, 33077 Bordeaux,France(e-mail: francis.chaouloff@bordeaux.inserm.fr)T
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