Reduced stress responsiveness in pregnancy: relationship with pattern of forebrain c-fos mRNA expression.
Stress-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis is known to be attenuated during late pregnancy and throughout lactation. To investigate the neural basis of this stress hyporesponsiveness we examined the changes in the restraint-induced HPA response and accompanying forebrain expression of c-fos mRNA that occur in rats between days 16 (D16) and 19 (D19) of gestation, times associated with declining levels of progesterone, a potential mediating factor. Compared to D16, the D19 group showed a significantly attenuated release of ACTH following 30min restraint. This reduced HPA response was accompanied by significantly lower levels of restraint-induced c-fos mRNA expression in the hypothalamic paraventricular nucleus. Other areas of the forebrain, including medial amygdala, piriform cortex, and ventrolateral septum, showed low c-fos mRNA expression in non-stressed (control) animals and a large increase following restraint, the magnitude of which was similar between D16 and D19 animals indicating no involvement in the differential HPA response to stress. However, a markedly different pattern of c-fos mRNA expression was observed in other brain areas, including barrel cortex and CA1 ventral and CA3 regions of the ventral hippocampus: D19 animals had low control expression which was increased by restraint, but D16 control animals had raised c-fos mRNA expression which was not further elevated by stress. These data demonstrate that region-specific changes in basal and stress-induced cellular activity occur during a period of late gestation coincident with attenuated HPA responsiveness. These changes in neuronal activity may contribute to the adaptive processes that prepare the mother for parturition and lactation.
Windle
Richard J
RJ
University Research Centre for Neuroendocrinology, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK.
Wood
Susan A
SA
Kershaw
Yvonne M
YM
Lightman
Stafford L
SL
Ingram
Colin D
CD
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D011247:Pregnancy / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000033:anatomy & histology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D012149:Restraint, Physical / Q000379:methods; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone