Behavior In Adult Offspring Research Articles

Hypothalamo-Pituitary-Adrenocortical Axis Function and Hedonic Behavior in Adult Male and Female Rats Prenatally Stressed by Maternal Food Restriction

Neuroendocrine activation during stress is affected by many factors contributing to the variability of the stress response. The present study was aimed at evaluating long-term changes in hypothalamo-pituitary-adrenocortical (HPA) axis function and in hedonic behavior in adult offspring prenatally stressed by maternal food restriction, with attention on possible gender differences. Adult offspring were blood sampled via a tail artery cannula. Prenatally stressed females had significantly higher adrenal weights compared to males. Plasma ACTH levels, which rose in response to acute stress induced by handling, were significantly higher in females compared to those in males. A similar pattern was found in plasma corticosterone. The rise in ACTH levels was more pronounced in prenatally stressed rats though the rise in corticosterone failed to be modified. Corticotropin releasing hormone (CRH) and proopiomelanocortin mRNA levels in the hypothalamic paraventricular nucleus and anterior pituitary, respectively, were found to be unchanged. The present experiments failed to reveal a decrease in hedonic behavior in prenatally stressed rats. In contrast, in male offspring a tendency to a higher sucrose preference was observed. These data together with observed changes in hormone and CRH mRNA levels indicate that the gestational stress used did not result in a depression-like state in adult offspring.

Inhibition of 11beta-hydroxysteroid dehydrogenase, the foeto-placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety-like behaviour in the offspring.

Glucocorticoids may underlie the association between prenatal stress, low birth weight and adult stress-associated disorders, e.g. hypertension and type 2 diabetes, increased hypothalamic-pituitary-adrenal (HPA) activity and affective dysfunction. Normally, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) rapidly inactivates glucocorticoids in placenta and many foetal tissues, thus acting as a 'barrier' to maternal steroids. We investigated the effect of inhibiting foeto-placental 11beta-HSD in rats, using carbenoxolone (CBX), on subsequent HPA activity and regulation and stress-induced behaviour in adult offspring. Pregnant Wistar rats were injected with CBX (12.5 mg s.c.) or vehicle daily throughout pregnancy. CBX treatment reduced birth weight. Adult offspring of CBX-treated dams had persistently reduced body weight, increased basal corticosterone (CORT) levels, increased corticotropin-releasing hormone (CRH) and reduced glucocorticoid receptor (GR) mRNA in the hypothalamic paraventricular nucleus, though hippocampal GR and mineralocorticoid receptor (MR) mRNA expression were unaltered. In addition, these animals showed less grooming and rearing in an open field and reduced immobility in a forced swim test, and had increased GR mRNA expression in the basolateral (BLA), central (CEA) and medial (MEA) nuclei of the amygdala, with unaltered MR mRNA. These data suggest that disturbance of the foeto-placental enzymatic barrier to maternal glucocorticoids reduces birth and body weight, and produces permanent alterations of the HPA axis and anxiety-like behaviour in aversive situations. The behavioural and HPA effects may reflect GR gene programming in amygdala and hypothalamus, respectively. Foetal overexposure to endogenous glucocorticoids (prenatal stress or reduced activity of foeto-placental 11beta-HSD) may represent a common link between the prenatal environment, foetal growth and adult neuroendocrine and affective disorders.

Prenatal dexamethasone exposure alters brain monoamine metabolism and adrenocortical response in rat offspring.

In this study, it has been clearly demonstrated that prenatal dexamethasone treatment (Dex; 0.05 mg/kg on gestational days 17, 18, and 19) resulted in the significant reductions of 5-hydroxytryptamine (5-HT) turnover in four brain regions, including the neocortex, hippocampus, hypothalamus, and midbrain + pons-medulla (M + P-M) but not in the striatum in the offspring at 3 and 14 wk of life, as well as dopamine turnover in the hypothalamus. [3H]paroxetine binding densities were increased in the hypothalamus and M + P-M at 14 wk of life, which corresponded to increased 5-HT contents in both regions. On the other hand, significantly lower norepinephrine contents in the neocortex and hippocampus were observed in the Dex group compared with the control group at 14 wk of life. In addition, the exposure to new environmental condition elevated blood corticosterone levels and enhanced behavioral activities to a greater extent in the Dex group than in controls at 7 wk of life, suggesting that elevated glucocorticoid levels during the pregnancy mimicked prenatal mild stress, producing developmental alterations in brain monoamine metabolism, endocrine response, and behavior in adult offspring.

Elevated plus-maze behavior in adult offspring of selectively bred rats

Animals sampled from the third generation (S3) of selective breeding of N:NIH strain rats based on ultrasonic vocalization (USV) rates in infancy (High, Low, and Random lines) were tested as adults on the elevated plus maze, a well-validated test of anxiety. Results showed that the Low line spent a greater percent of time in the open arms of the maze than High and Random (control) line animals, and a lower percent of time exploring from a relatively more protected position. There were no significant sex differences. The present study represents a probe into the processes at work during the early stages of selection for infant USV, and suggests that an adult measure of anxiety may be affected by selection for this infantile behavior.

Periodic maternal deprivation alters stress response in adult offspring: Potentiates the negative feedback regulation of restraint stress-induced adrenocortical response and reduces the frequencies of open field-induced behaviors

The effects of periodic maternal deprivation (PMD) treatment on the adrenocortical stress response and on open-field behavior in adult offspring were investigated. Sprague-Dawley rat pups were deprived of mothers daily for 4.5 h during the first 3 weeks of life. PMD treatment resulted in lower corticosterone levels during restraint stress later in life. The result of dexamethasone suppression test indicated that PMD treatment caused a potentiation of the negative feedback function of adrenocortical response. These effects of PMD were not accompanied by an increased density of the hippocampal glucocorticoid receptor which has been reported to be induced in neonatal handling treatment (brief 15-min maternal deprivation). Serotonin (5-HT)-2 and β-adrenergic binding sites were also examined in cerebral cortex and no change of binding capacities were induced by PMD treatment. In the open-field test, PMD treatment decreased the number of ambulations and rearings but did not affect a frequency of defecation. From these results, it is suggested that PMD treatment leads rats to be insensitive to environmental stimuli in adulthood.

Effect of maternal cadmium exposure on postnatal development and tissue cadmium, copper and zinc concentrations in rats.

Administration of 60 ppm cadmium (Cd) in drinking water from the 1st to the 20th day of gestation to female rats did not affect the viability, body weight gain, food, and water consumption of offspring. The blood hemoglobin level was reduced in 2-week-old females and males but not in 16-week-old offspring. Hematocrit and serum glucose level were not affected at either age. Cadmium concentration in the intestinal wall was increased in both age groups, with marginal uptake in other organs. A decrease in copper (Cu) concentration was found in the brain of 2-week-old offspring of both sexes and of 16-week-old females. The brain zinc (Zn) concentration was decreased only in 16-week-old animals. The physical and neuromuscular development of offspring before weaning was not impaired by maternal Cd treatment. The alterations in Cu and Zn metabolism were associated with reduced locomotor activity and affected open-field behavior in adult offspring of either sex and with decreased avoidance acquisition in adult female offspring. The results obtained suggest a relationship between the reduced brain Cu and Zn levels and CNS dysfunction in adult offspring of female rats exposed to Cd during gestation.