Neurodevelopment milestone abnormalities in rats exposed to stress in early life

Manipulation of the corticosteroid milieu by interfering
with the mother–newborn relationship has received
much attention because of its potential bearing on psychopathology
later in life. In the present study, infant rats that
were deprived of maternal contact between the 2nd and the
15th postnatal days (MS2–15) for 6 h/day were subjected to a
systematic assessment of neurodevelopmental milestones
between postnatal days 2 and 21. The analyses included
measurements of physical growth and maturation and evaluation
of neurological reflexes. Although some somatic milestones
(e.g. eye opening) were anticipated, MS2–15 animals
showed retardation in the acquisition of postural reflex, air
righting and surface righting reflexes, and in the wire suspension
test; the latter two abnormalities were only found in
males. A gender effect was also observed in negative
geotaxis, with retardation being observed in females but not
males. To better understand the delay of neurological maturation
in MS2–15 rats, we determined the levels of various
monoamines in different regions of the brain stem, including
the vestibular area, the substantia nigra, ventral tegmental
area and dorsal raphe nuclei. In the vestibular region of
MS2–15 rats the levels of 5-HT were reduced, while 5-HT turnover
was increased. There was also a significant increase of
the 5-HT turnover in MS2–15 animals in the raphe nuclei,
mainly due to increased 5-hydroxyindoleacetic acid (5-HIAA)
levels, and an increase of 3,4-dihydroxyphenylacetic acid
(DOPAC) levels in the ventral tegmental area (VTA) of
stressed females. No significant differences were found in
the immunohistochemical sections for tyrosine and tryptophan
hydroxylase in these regions of the brain stem. In conclusion,
the present results show that postnatal stress induces
signs of neurological pathology that may contribute to
the genesis of behavioral abnormalities later in life.
Fundação para a Ciência e a Tecnologia (FCT)