Anxiety-like behaviour and associated neurochemical and endocrinological alterations in male pups exposed to prenatal stress
Psychoneuroendocrinology. 2012-10-01; 37(10): 1646-1658
DOI: 10.1016/j.psyneuen.2012.02.010
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Epidemiological studies suggest that emotional liability in infancy could be a
predictor of anxiety-related disorders in the adulthood. Rats exposed to prenatal
restraint stress (“PRS rats”) represent a valuable model for the study of the
interplay between environmental triggers and neurodevelopment in the pathogenesis
of anxious/depressive like behaviours. Repeated episodes of restraint stress were
delivered to female Sprague-Dawley rats during pregnancy and male offspring were
studied. Ultrasonic vocalization (USV) was assessed in pups under different
behavioural paradigms. After weaning, anxiety was measured by conventional tests.
Expression of GABA(A) receptor subunits and metabotropic glutamate (mGlu)
receptors was assessed by immunoblotting. Plasma leptin levels were measured
using a LINCOplex bead assay kit. The offspring of stressed dams emitted more
USVs in response to isolation from their mothers and showed a later suppression
of USV production when exposed to an unfamiliar male odour, indicating a
pronounced anxiety-like profile. Anxiety like behaviour in PRS pups persisted one
day after weaning. PRS pups did not show the plasma peak in leptin levels that is
otherwise seen at PND14. In addition, PRS pups showed a reduced expression of the
γ2 subunit of GABA(A) receptors in the amygdala at PND14 and PND22, an increased
expression of mGlu5 receptors in the amygdala at PND22, a reduced expression of
mGlu5 receptors in the hippocampus at PND14 and PND22, and a reduced expression
of mGlu2/3 receptors in the hippocampus at PND22. These data offer a clear-cut
demonstration that the early programming triggered by PRS could be already
translated into anxiety-like behaviour during early postnatal life.