Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats

Abstract

Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Although central oxytocin has antistress effects, the role of central oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric emptying was measured in rats receiving acute restraint stress, 5 consecutive days of repeated restraint stress (chronic homotypic stress), and 7 consecutive days of varying types of stress (chronic heterotypic stress). Oxytocin and oxytocin receptor antagonist were administered intracerebroventricularly (icv). Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT-PCR. The changes of oxytocinergic neurons in the PVN were evaluated by immunohistochemistry. Acute stress delayed gastric emptying, and the delayed gastric emptying was completely restored after 5 consecutive days of chronic homotypic stress. In contrast, delayed gastric emptying persisted following chronic heterotypic stress. The restored gastric emptying following chronic homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv injection of oxytocin restored delayed gastric emptying induced by chronic heterotypic stress. CRF mRNA expression, which was significantly increased in response to acute stress and chronic heterotypic stress, returned to the basal levels following chronic homotypic stress. In contrast, oxytocin mRNA expression was significantly increased following chronic homotypic stress. The number of oxytocin-immunoreactive cells was increased following chronic homotypic stress at the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA expression induced by acute stress and chronic heterotypic stress. It is suggested that the adaptation mechanism to chronic stress may involve the upregulation of oxytocin expression in the hypothalamus, which in turn attenuates CRF expression.

Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit

“…Oxytocin wird zentral im PVN als Reaktion auf Stress ausgeschüttet, um die Stressreaktion abzudämpfen [32] [33]. Darüber hinaus weisen die Oxytocin-mRNA-und CRF-mRNAExpression im PVN nach akuter und auch chronischer Stressexposition eine negative Korrelation auf.…”

“…Darüber hinaus weisen die Oxytocin-mRNA-und CRF-mRNAExpression im PVN nach akuter und auch chronischer Stressexposition eine negative Korrelation auf. Hohe Oxytocinspiegel sind demnach mit erniedrigten CRFSpiegeln assoziiert [32].…”

“…Daher liegt der Schluss nahe, dass die Hemmung der CRF-Neuronen nicht auf direktem Wege erfolgt [34]. Intracerebroventrikuläre Gabe von Oxytocin hemmt die CRF-Expression im PVN [30,32,34]. Dieser Effekt kann durch die Gabe eines γ-Aminobuttersäure(GABA)-Antagonisten verhindert werden [34].…”

Anti-stress Effect of Hypothalamic Oxytocin, Importance of Somatosensory Stimulation and Social Buffering

“…In the central amygdala, others also showed that OXT enhances GABAergic transmission through an increased frequency of the inhibitory postsynaptic currents [14] . Central-injection of OXT, but not peripheral-injection of OXT, significantly improves delayed gastric emptying induced by acute restraint stress in mice [16] and rats [11] . Similarly, water avoidance stress-induced acceleration of colonic motility is attenuated by central, but not peripheral, administration of OXT [17] .…”

“…OXT attenuates HPA axis in response to stress [10] . Delayed gastric emptying and accelerated colonic transit induced by acute restraint stress are abolished by intracerebroventricular (icv)-injection of OXT in rats [11,12] . Anti-stress and anti-anxiety effects of OXT are mediated by its inhibitory effect on CRF mRNA expression [13] .…”