Effects of maternal l-tryptophan depletion and corticosterone administration on neurobehavioral adjustments in mouse dams and their adolescent and adult daughters

Francesca Zoratto, Alessandra Berry, Francesca Anzidei, Marco Fiore, Enrico Alleva, Giovanni Laviola, Simone Macrì

Research output: Contribution to journalArticle

Abstract

Major depressive disorder (MDD), a pathology characterized by mood and neurovegetative disturbances, depends on a multi-factorial contribution of individual predisposition (e.g., diminished serotonergic transmission) and environmental factors (e.g., neonatal abuse or neglect). Despite its female-biased prevalence, MDD basic research has mainly focused on male rodents. Most of present models of depression are also devalued due to the fact that they typically address only one of the aforementioned pathogenetic factors. In this paper we first describe the basic principles behind mouse model development and evaluation and then articulate that current models of depression are intrinsically devalued due to poor construct and/or external validity. We then report a first attempt to overcome this limitation through the design of a mouse model in which the genetic and the environmental components of early risk factors for depression are mimicked together. Environmental stress is mimicked through the supplementation of corticosterone in the maternal drinking water while biological predisposition is mimicked through maternal access to an l-tryptophan (the serotonin precursor) deficient diet during the first week of lactation. CD1 dams and their offspring exposed to the l-tryptophan deficient diet (T) and to corticosterone (80. mg/l; C) were compared to animal facility reared (AFR) subjects. T and C mice served as intermediate reference groups. Adolescent TC offspring, compared to AFR mice, showed decreased time spent floating in the forced-swim test and increased time spent in the open sectors of an elevated 0-maze. Adult TC offspring showed reduced preference for novelty, decreased breakpoints in the progressive ratio operant procedure and major alterations in central BDNF levels and altered HPA regulation.The route of administration and the possibility to control the independent variables predisposing to depressive-like symptoms disclose novel avenues towards the development of animal models with increased external and construct validity. Furthermore, the observation that, compared to adult subjects, adolescent mice display an opposite profile suggests that peri-pubertal developmental processes may interact with neonatal predispositions to calibrate the adult abnormal phenotype.

Original languageEnglish
Pages (from-to)1479-1492
Number of pages14
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume35
Issue number6
DOIs
Publication statusPublished - Aug 1 2011

Keywords

  • Animal models
  • Construct validity
  • Depression
  • Early risk factors
  • External validity
  • Stress

ASJC Scopus subject areas

  • Biological Psychiatry
  • Pharmacology

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