Effects of early-life stress on serotonin(1A) receptors in juvenile Rhesus monkeys measured by positron emission tomography

Biol Psychiatry. 2010 Jun 15;67(12):1146-53. doi: 10.1016/j.biopsych.2009.12.030. Epub 2010 Feb 20.

Abstract

Background: Traumatic experiences in early childhood are associated with increased risk for developing mood and anxiety disorders later in life. Low serotonin(1A) receptor (5-HT(1A)R) density during development has been proposed as a trait-like characteristic leading to increased vulnerability of stress-related neuropsychiatric disorders.

Methods: To assess the relationship between early-life stress and alterations in the serotonin system during development, we used positron emission tomography to measure in vivo 5-HT(1A)R density and apparent dissociation constant (K(D)(app)) in the brain of juvenile Rhesus monkeys exposed to the early-life stress of peer-rearing.

Results: In general, 5-HT(1A)R density and K(D)(app) were decreased in peer-reared compared with control mother-reared animals. However, increase in receptor density was found in the dorsomedial prefrontal cortex of peer-reared females.

Conclusions: These findings suggest that exposure to an adverse early-life environment during infancy is associated with long-term alterations in the serotonin system and support previous studies suggesting that reduced 5-HT(1A)R density during development might be a factor increasing vulnerability to stress-related neuropsychiatric disorders. Furthermore, alterations in the serotonin system seemed to be gender- and region-specific, providing a biological basis for the higher prevalence of affective disorders in women.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Female
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Macaca mulatta
  • Male
  • Maternal Deprivation*
  • Piperazines / analysis
  • Positron-Emission Tomography / methods*
  • Pyrimidines / analysis
  • Radioligand Assay / methods
  • Random Allocation
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin Antagonists / analysis
  • Sex Characteristics
  • Stress, Psychological / metabolism*

Substances

  • 4-fluoro-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyrimidinyl)benzamide
  • Piperazines
  • Pyrimidines
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • Hydroxyindoleacetic Acid