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. 2010 Mar;52(2):121-32.
doi: 10.1002/dev.20419.

Effects of excessive glucocorticoid receptor stimulation during early gestation on psychomotor and social behavior in the rat

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Effects of excessive glucocorticoid receptor stimulation during early gestation on psychomotor and social behavior in the rat

Karine Kleinhaus et al. Dev Psychobiol. 2010 Mar.

Abstract

Severe psychological stress in the first trimester of pregnancy increases the risk of schizophrenia in the offspring. To begin to investigate the role of glucocorticoid receptors in this association, we determined the effects of the glucocorticoid dexamethasone (2 mg/kg), administered to pregnant rats on gestation days 6-8, on maternal behaviors and schizophrenia-relevant behaviors in the offspring. Dams receiving dexamethasone exhibited increased milk ejection bouts during nursing. Offspring of dexamethasone-treated dams (DEX) showed decreased juvenile social play and a blunted acoustic startle reflex in adolescence and adulthood, effects that were predicted by frequency of milk ejections in the dams. DEX offspring also showed increased prepulse inhibition of startle and reduced amphetamine-induced motor activity, effects not correlated with maternal behavior. It is postulated that over-stimulation of receptors targeted by glucocorticoids in the placenta or other maternal tissues during early gestation can lead to psychomotor and social behavioral deficits in the offspring. Moreover, some of these deficits may be mediated by alterations in postnatal maternal behavior and physiology produced by early gestational exposure to excess glucocorticoids.

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Figures

FIGURE 1
FIGURE 1
Social play behaviors in juvenile offspring of dams treated with saline (CON; n = 6; white bars) or DEX (n = 5; black bars). Bars show litter means (±SEM) for the number of walkovers (A) and pins (B) per a 10-min period of interaction between two same-sexed littermates. DEX offspring showed decreases in play behavior. *p < .05, tp = .16.
FIGURE 2
FIGURE 2
Acoustic startle reflex (A and B) and prepulse inhibition of startle (PPI) (C and D) in offspring of dams treated with saline (CON; gray symbols) or DEX (black symbols) during early gestation. Offspring were tested during late adolescence (A and C) or in adulthood (B and D) (see text). Panels A and B show the increase in the startle reflex (Newtons) as a function of startle stimulus loudness (dB; difference from background of 60 dB). Maximum startle amplitude (reflex capacity) was significantly decreased in DEX offspring. Panels C and D show increasing inhibition of the startle reflex as a function of the loudness (dB, difference from background) of the prepulse stimulus delivered 100 ms prior to the startle stimulus. DEX offspring showed a significant increase in the maximal level of prepulse inhibition and in the efficiency of PPI, defined as the slope within the dynamic range of the prepulse loudness-reflex inhibition function (see the Methods Section). *p < .05, main effect of prenatal DEX on maximum response; #p < .05, main effect of prenatal DEX on slope.
FIGURE 3
FIGURE 3
Average ambulation (A) and stereotypy (B) following injection of .0 (saline), 1.0 or 5.0 mg/kg amphetamine. DEX offspring show decreases in these measures of motor activity. For main effect of prenatal DEX treatment: *p < .05. For dose comparisons: #p < .05 relative to saline, @p < .05 relative to 1.0 mg/kg dose.

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