Increased vulnerability to psychosocial stress in heterozygous serotonin transporter knockout mice

Alessandro Bartolomucci, Valeria Carola, Tiziana Pascucci, Stefano Puglisi-Allegra, Simona Cabib, Klaus Peter Lesch, Stefano Parmigiani, Paola Palanza, Cornelius Gross

Research output: Contribution to journalArticle

Abstract

Epidemiological evidence links exposure to stressful life events with increased risk for mental illness. However, there is significant individual variability in vulnerability to environmental risk factors, and genetic variation is thought to play a major role in determining who will become ill. Several studies have shown, for example, that individuals carrying the S (short) allele of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) have an increased risk for major depression following exposure to stress in adulthood. Identifying the molecular mechanisms underlying this gene-by-environment risk factor could help our understanding of the individual differences in resilience to stress. Here, we present a mouse model of the 5-HTT-by-stress risk factor. Wild-type and heterozygous 5-HTT knockout male mice were subjected to three weeks of chronic psychosocial stress. The 5-HTT genotype did not affect the physiological consequences of stress as measured by changes in body temperature, body weight gain and plasma corticosterone. However, when compared with wild-type littermates, heterozygous 5-HTT knockout mice experiencing high levels of stressful life events showed significantly depressed locomotor activity and increased social avoidance toward an unfamiliar male in a novel environment. Heterozygous 5-HTT knockout mice exposed to high stress also showed significantly lower levels of serotonin turnover than wild-type littermates, selectively in the frontal cortex, which is a structure that is known to control fear and avoidance responses, and that is implicated in susceptibility to depression. These data may serve as a useful animal model for better understanding the increased vulnerability to stress reported in individuals carrying the 5-HTTLPR S allele, and suggest that social avoidance represents a behavioral endophenotype of the interaction between 5-HTT and stress.

Original languageEnglish
Pages (from-to)459-470
Number of pages12
JournalDMM Disease Models and Mechanisms
Volume3
Issue number7-8
DOIs
Publication statusPublished - 2010

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Knockout Mice
Alleles
Body Temperature Changes
Depression
Genes
Endophenotypes
Frontal Lobe
Locomotion
Corticosterone
Individuality
Weight Gain
Fear
Serotonin
Animal Models
Genotype
Body Weight
Animals
Plasmas

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Neuroscience (miscellaneous)
  • Medicine(all)

Cite this

Increased vulnerability to psychosocial stress in heterozygous serotonin transporter knockout mice. / Bartolomucci, Alessandro; Carola, Valeria; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Cabib, Simona; Lesch, Klaus Peter; Parmigiani, Stefano; Palanza, Paola; Gross, Cornelius.

In: DMM Disease Models and Mechanisms, Vol. 3, No. 7-8, 2010, p. 459-470.

Research output: Contribution to journalArticle

Bartolomucci, Alessandro ; Carola, Valeria ; Pascucci, Tiziana ; Puglisi-Allegra, Stefano ; Cabib, Simona ; Lesch, Klaus Peter ; Parmigiani, Stefano ; Palanza, Paola ; Gross, Cornelius. / Increased vulnerability to psychosocial stress in heterozygous serotonin transporter knockout mice. In: DMM Disease Models and Mechanisms. 2010 ; Vol. 3, No. 7-8. pp. 459-470.
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