Long-term behavioural and molecular alterations associated with maternal separation in rats

Melanie Lippmann, Aaron Bress, Charles Nemeroff, Paul M. Plotsky, Lisa M. Monteggia

Research output: Contribution to journalArticle

234 Citations (Scopus)

Abstract

In this study we addressed whether certain behavioural measures, endocrine levels and specific stress-related proteins exhibit long-term alterations in adult rats following repeated postnatal maternal separation. Rats were subjected to daily maternal separation for 15 min (HMS15) or 180 min (HMS180) from postnatal day 2-14. Adult HMS180 animals were hypoactive and had increased levels of stereotypy compared to HMS15 and normal animal facility-reared (AFR) animals. HMS180 animals also had augmented plasma adrenocorticotropin (ACTH) and corticosterone (CORT) concentrations following an acute stressor, compared to the other two groups. We assessed persistent changes in proteins regulated by stress in hippocampus, cortex, ventral tegmental area, nucleus accumbens, striatum and amygdala. Western blotting analysis revealed a decrease in the levels of mature brain-derived neurotrophic factor (BDNF) in hippocampus and striatum, but an increase in the ventral tegmental area in the HMS180 rats. Levels of pro-BDNF were significantly increased in the ventral tegmental area of HMS180 animals but were unchanged in other brain regions compared to the other two groups. Levels of the transcription factors cAMP response element binding protein (CREB) and ΔFosB were unchanged in all of the brain regions studied in the maternally separated rats. These data show that maternal separation induces long-term changes in BDNF expression, and more specifically the processing of BDNF, in the hippocampus, striatum and ventral tegmental area. Recognition of these adaptations begins to define the brain regions, and neural circuitry, associated with persistent alterations induced by early life stressors and the development of mood disorders.

Original languageEnglish
Pages (from-to)3091-3098
Number of pages8
JournalEuropean Journal of Neuroscience
Volume25
Issue number10
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Ventral Tegmental Area
Brain-Derived Neurotrophic Factor
Mothers
Hippocampus
Heat-Shock Proteins
Adrenocorticotropic Hormone
Brain
Tegmentum Mesencephali
Cyclic AMP Response Element-Binding Protein
Nucleus Accumbens
Corticosterone
Amygdala
Mood Disorders
Transcription Factors
Western Blotting

Keywords

  • ΔFosB
  • Adrenocorticotropin
  • BDNF
  • Corticosterone
  • CREB
  • Depression
  • Hippocampus
  • Stress

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Long-term behavioural and molecular alterations associated with maternal separation in rats. / Lippmann, Melanie; Bress, Aaron; Nemeroff, Charles; Plotsky, Paul M.; Monteggia, Lisa M.

In: European Journal of Neuroscience, Vol. 25, No. 10, 01.05.2007, p. 3091-3098.

Research output: Contribution to journalArticle

Lippmann, Melanie ; Bress, Aaron ; Nemeroff, Charles ; Plotsky, Paul M. ; Monteggia, Lisa M. / Long-term behavioural and molecular alterations associated with maternal separation in rats. In: European Journal of Neuroscience. 2007 ; Vol. 25, No. 10. pp. 3091-3098.
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