Gonadal steroid modulation of stress-induced hypothalamo-pituitary-adrenal activity and anxiety behavior: role of central oxytocin.
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 [(125)I]d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr-NH(2)(9)]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 desGlyNH(2), d(CH(2))(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.
Windle
Richard J
RJ
Human and Clinical Sciences Research Center, University of Nottingham, Queen's Medical Center, UK. richard.windle@nottingham.ac.uk
Gamble
Lisa E
LE
Kershaw
Yvonne M
YM
Wood
Susan A
SA
Lightman
Stafford L
SL
Ingram
Colin D
CD
D000311:Adrenal Glands / Q000473:pathology*; D000818:Animals; D001007:Anxiety; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology*; D008024:Ligands; D018377:Neurotransmitter Agents; D010121:Oxytocin / Q000378:metabolism*; D010902:Pituitary Gland / Q000473:pathology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D013997:Time Factors
D008024:Ligands; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D013256:Steroids; D011374:Progesterone; D010121:Oxytocin