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Article
Gender specific effect of neonatal handling on stress reactivity of adolescent rats.
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Year: 2003

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Abstract

Early neonatal handling of rat pups produces dampened hypothalamic-pituitary-adrenal axis reactivity to stress in adult male offspring. However, less is known about whether there is a similar effect for females. Although, most studies of neonatal handling have examined subsequent effects during adulthood, adolescence is an important developmental stage for stress responsivity. To address these issues, the effect of neonatal handling on the endocrine stress response and brain activity of male and female rats was determined in response to acute restraint stress during adolescence. Consistent with previous findings in adult males, neonatal handling reduced restraint stress-induced hormone levels in adolescent males. However, in contrast, we found elevated plasma hormone concentrations in handled females. A gender-specific handling effect on brain activity was also evident, with significantly increased stress-induced activation of the posterior cingulate cortex of handled females, as measured by c-fos mRNA expression. The striking gender difference in the effect of early neonatal handling provides evidence that this must be considered as an important variable in subsequent stress responsivity induced by early manipulations.


Article
Long-term effects of a single exposure to immobilization stress on the hypothalamic-pituitary-adrenal axis: transcriptional evidence for a progressive desensitization process.

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Abstract In the present work we have characterized the long-term influence of a single exposure to the stress of immobilization (IMO) on the hypothalamic-pituitary-adrenal (HPA) axis of adult rats. Rats without prior stress (control) and rats exposed to IMO for 2 h on day 1 (IMO+4wk) or on day 21 (IMO+1wk) were killed on day 28, either without stress (basal), immediately after IMO for 1 h (IMO), or 1 h after termination of IMO (post-IMO). IMO caused a strong activation of c-fos mRNA and corticotropin-releasing factor (CRF) and vasopressin (AVP) heteronuclear RNA (hnRNA) in the paraventricular nucleus of the hypothalamus in control rats; this activation was essentially maintained in the post-IMO period. The overall AVP hnRNA response to day 28 stress was not affected by prior stress. Post-IMO c-fos mRNA and CRF hnRNA levels were lower in previously stressed rats, as compared with controls. Whereas the effect of prior IMO on both peripheral HPA hormones and c-fos mRNA was maximal in IMO+1wk rats, the effect of prior stress on CRF hnRNA was only observed in IMO+4wk rats. The present data indicate that prior single IMO triggers a process of desensitization of the HPA responsiveness to IMO over the course of the following weeks. Although the various components of the HPA axis were modified in the same direction, a clear temporal dissociation was found among them, revealing the fine tuning of stress-induced activation of the HPA axis


Article
The magnocellular oxytocin system, the fount of maternity: adaptations in pregnancy.
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Year: 2003

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Oxytocin secretion from the posterior pituitary gland is increased during parturition, stimulated by the uterine contractions that forcefully expel the fetuses. Since oxytocin stimulates further contractions of the uterus, which is exquisitely sensitive to oxytocin at the end of pregnancy, a positive feedback loop is activated. The neural pathway that drives oxytocin neurons via a brainstem relay has been partially characterised, and involves A2 noradrenergic cells in the brainstem. Until close to term the responsiveness of oxytocin neurons is restrained by neuroactive steroid metabolites of progesterone that potentiate GABA inhibitory mechanisms. As parturition approaches, and this inhibition fades as progesterone secretion collapses, a central opioid inhibitory mechanism is activated that restrains the excitation of oxytocin cells by brainstem inputs. This opioid restraint is the predominant damper of oxytocin cells before and during parturition, limiting stimulation by extraneous stimuli, and perhaps facilitating optimal spacing of births and economical use of the store of oxytocin accumulated during pregnancy. During parturition, oxytocin cells increase their basal activity, and hence oxytocin secretion increases. In addition, the oxytocin cells discharge a burst of action potentials as each fetus passes through the birth canal. Each burst causes the secretion of a pulse of oxytocin, which sharply increases uterine tone; these bursts depend upon auto-stimulation by oxytocin released from the dendrites of the magnocellular neurons in the supraoptic and paraventricular nuclei. With the exception of the opioid mechanism that emerges to restrain oxytocin cell responsiveness, the behavior of oxytocin cells and their inputs in pregnancy and parturition is explicable from the effects of hormones of pregnancy (relaxin, estrogen, progesterone) on pre-existing mechanisms, leading through relative quiescence at term inter alia to net increase in oxytocin storage, and re

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