Effects of early-life stress on serotonin(1A) receptors in juvenile Rhesus monkeys measured by positron emission tomography.
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.
Spinelli
Simona
S
National Institute on Alcohol Abuse and Alcoholism, Poolesville, MD, USA. spinellis@kennedykrieger.org
Chefer
Svetlana
S
Carson
Richard E
RE
Jagoda
Elaine
E
Lang
Lixin
L
Heilig
Markus
M
Barr
Christina S
CS
Suomi
Stephen J
SJ
Higley
J Dee
JD
Stein
Elliot A
EA
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008253:Macaca mulatta; D008297:Male; D008426:Maternal Deprivation; D010879:Piperazines / Q000032:analysis; D049268:Positron-Emission Tomography / Q000379:methods*; D011743:Pyrimidines / Q000032:analysis; D011869:Radioligand Assay / Q000379:methods; D011897:Random Allocation; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000032:analysis; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000378:metabolism*
C520057:4-fluoro-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyrimidinyl)benzamide; D010879:Piperazines; D011743:Pyrimidines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D006897:Hydroxyindoleacetic Acid