Journal
ENDOCRINOLOGY
Volume 147, Issue 5, Pages 2423-2431Publisher
ENDOCRINE SOC
DOI: 10.1210/en.2005-1079
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Funding
- Biotechnology and Biological Sciences Research Council [BB/C51297X/1] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BB/C51297X/1] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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Intracerebroventricular administration of oxytocin reduces anxiety behavior and hypothalamo-pituitary-adrenal (HPA) responses to stress in female rats. Similar changes are seen in late-pregnant rats, and oxytocin-sensitive pathways may mediate these effects. This study investigated anxiety behavior and stress responses using a gonadal steroid model of late pregnancy, which is known to increase endogenous oxytocin expression. Compared with continuous progesterone treatment, 3-d withdrawal of progesterone after 11-d treatment of ovariectomized rats with estradiol and progesterone resulted in increased binding of the oxytocin receptor ligand [I-125]d(CH2)(5)[Tyr(Me)(2), Thr(4), Tyr-NH29] ornithine vasotocin in selective forebrain regions, including the ventrolateral septum and ventromedial hypothalamus. Behavior in the elevated plus-maze indicated that progesterone withdrawal had an anxiolytic effect, and this was associated with lower levels of c-fos mRNA expression in the ventral hippocampus, an area previously shown to be sensitive to oxytocin. In other groups of animals, the plasma corticosterone response to a psychological stress (10 min of 114 dB white noise) was significantly attenuated by this steroid manipulation. Furthermore, simultaneous infusion of the selective oxytocin receptor antagonist desGly-NH2, d(CH2)(5)[Tyr(Me)(2), Thr(4)] OVT during the period of progesterone withdrawal reversed this attenuation of noise-induced HPA activation, indicating a role for endogenous oxytocin in this effect. Thus, mimicking the steroid profile of late pregnancy leads to a reduction in anxiety behavior and attenuates HPA activity induced by mild stress. These effects appear to be mediated through the involvement of central oxytocin neurotransmission.
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