Gonadal Steroid Modulation of Stress-Induced Hypothalamo-Pituitary-Adrenal Activity and Anxiety Behavior: Role of Central Oxytocin

Abstract

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.

Intracerebroventricularly Administered Oxytocin Attenuated Cortisol Secretion, but not Behavioral Responses, during Isolation in Holstein Steers

“…The anti-anxiolytic effect of oxytocin knockout has not been confirmed in males [1,20]. In addition, central oxytocin activity to attenuate anxiety response to a mild stressor might be under the strong regulation of gonadal steroid in mice and rats [17], suggesting a strong relation between oxytocin and gonadal steroids. No inhibition of behavioral response to isolation by oxytocin in this study also may have been due to lower estrogen influence in steers castrated before sexual maturation than that in females.…”

Effects of Chronic Intracerebral Prolactin on the Oxytocinergic and Vasopressinergic System of Virgin Ovariectomized Rats

“…Also, the E 2 replacement applied in the present study has been shown to result in equal proestrus-resembling plasma E 2 concentrations in both vehicle- and PRL-treated animals [8]. This is crucial as gonadal steroids were found to influence hypophyseal PRL secretion [51], expression of PRL receptors in the brain [52,53,54], neuronal c- fos stress responses [55] as well as the activity of the OXT system [56,57,58]. However, future experiments are needed to demonstrate if estrogens play a permissive role for the observed effects.…”

The Meaning of Weaning: Influence of the Weaning Period on Behavioral Development in Mice

“…In males, the VMH is critical in the regulation of sexual and aggressive behaviors primarily through the actions of estrogen on ER ␣ [Harding and McGinnis, 2004;Nelson and Trainor, 2007]. OT receptor expression in the VMH is up-regulated following increases in estradiol [Bale et al, 2001] or decreases in progesterone [Windle et al, 2006], and estrogen and oxytocin receptor mRNA is found to be co-expressed in VMH neurons [Devidze et al, 2005]. Taken together with our data, these findings suggest that variation in maternal care across the whole of the postnatal period can induce changes in offspring reproductive strategies.…”