What is Oxytocin?
Oxytocin is a hormone and neuropeptide formed in the hypothalamus.[1] Oxytocin has been used in medicine since 1911 to help induce uterine contractions during pregnancy.[2],[3] Oxytocin’s role in pregnancy and delivery has been well studied, but there is an increasing body of evidence to support its role in the stress response and the HPA axis.
Influence of Stress on Oxytocin
Both human and rat studies of oxytocin show that various types of stress, including psychological and social stress, lead to increased oxytocin secretion and higher oxytocin levels in the blood.[4],[5],[6] Several studies show oxytocin to have an anxiolytic effect in stressful situations. Cortisol and norepinephrine increase blood pressure and activate the body’s physical response to stress. In animal studies, increased oxytocin is associated with decreased cortisol, decreased norepinephrine, and decreased blood pressure.[7],[8] Lactating women (i.e. women with higher oxytocin levels) also have decreased cortisol responses to physical stress.[9]
Brain areas that are heavily involved in the stress response include the hippocampus and amygdala.[10],[11],[12] Oxytocin can affect these specific brain areas in ways that improve physiological and behavioral responses to stress.
Oxytocin and Memory
Animal research shows that oxytocin can protect hippocampal memory from the damaging effects of stress. Scientists think that under uncontrollable stress, animals and humans learn that their actions have no effect on a negative outcome.[13] This “learned helplessness” can have a detrimental effect on long-term health.[14] For example, scientists find that rats exposed to uncontrollable shocks perform poorly on hippocampal memory tasks, and their hippocampi show changes related to decreased learning and depression.[15] To test oxytocin’s effects on this type of stress, researchers subjected rats to a Morris water maze task (a type of uncontrollable stress). Some rats were given intranasal oxytocin while some were not.[16] The researchers found that rats given oxytocin had decreased damage to hippocampal memory and learning in the presence of uncontrollable stress.[17]
Oxytocin and the HPA Axis
The amygdala is another area of the brain important for regulating behavioral responses to stress. It is also particularly rich in oxytocinergic neurons and receptors.[18] Scientists have found that blocking oxytocin receptors in the amygdala results in altered emotions as well as increased activity of the HPA axis.[19] Ebner et. al. induced physical stress in rats by forcing them to swim. They found that forced swimming caused a significant increase in oxytocin levels in the amygdala.[20] Animals treated with a substance that blocks oxytocin spent more time swimming and less time floating in the water.[21] This suggests that oxytocin promotes “passive” stress coping strategies, and that its calming effects prevent an overactive stress response.[22] Furthermore, rats treated with the oxytocin blockade had increased levels of the excitatory neurotransmitters glutamate and aspartate, which indicates that oxytocin has inhibitory effects in the brain.[23]
Oxytocin, Anxiety, and Stress-Related Diseases
What do all these studies about stressed out rats mean for us? They show that oxytocin administration in humans could potentially help treat stress-related diseases such as PTSD, depression, and anxiety. Intranasal oxytocin is the preferred delivery method in humans because it is safe and non-invasive.[24] Intranasal oxytocin (IN OT) is delivered to the olfactory bulbs and the brain stem which are connected to the amygdala by GABA neurons; therefore, IN OT can mimic biological oxytocin release in the brain.[25] IN OT has anxiety reducing effects, primarily by regulating serotonin signaling in the amygdala.[26]
IN OT experiments in humans demonstrate that oxytocin can reduce social stress. In the setting of a mock job interview, IN OT was shown to reduce anxiety and cortisol release in participants.[27] Meta-analysis of multiple IN OT studies in humans show that IN OT is associated with increased social behavior, communication, trust, and willingness to share emotions.[28] Although continued research is necessary to validate these findings, it appears as though oxytocin could help reduce stress and anxiety, as well as the facilitate positive social connection that is crucial for emotional and physical well-being.
References:
[1] Lippert TH, Mueck AO, Seeger H, & Pfaff A. (2003). Effects of oxytocin outside pregnancy. Hormone Research in Paediatrics, 60(6), 262-271.
[2] Olff M, Frijling JL, Kubzansky LD, et. al. (2013). The role of oxytocin in social bonding, stress regulation and mental health: an update on the moderating effects of context and interindividual differences. Psychoneuroendocrinology, 38(9), 1883-1894.
[3] Lippert op. cit.
[4] Lippert op. cit.
[5] Olff op. cit.
[6] Ebner K, Bosch OJ, Krömer SA, et. al. (2005). Release of oxytocin in the rat central amygdala modulates stress-coping behavior and the release of excitatory amino acids. Neuropsychopharmacology, 30(2), 223.
[7] Lippert op. cit.
[8] Olff op. cit.
[9] Olff op. cit.
[10] Sippel LM, Allington CE, Pietrzak RH, et. al. (2017). Oxytocin and Stress-related Disorders: Neurobiological Mechanisms and Treatment Opportunities. Chronic Stress, 1, 2470547016687996.
[11] Lee SY, Park SH, Chung C, et. al. (2015). Oxytocin protects hippocampal memory and plasticity from uncontrollable stress. Scientific reports, 5, 18540.
[12] Ebner K, Bosch OJ, Krömer SA, et.al. (2005). Release of oxytocin in the rat central amygdala modulates stress-coping behavior and the release of excitatory amino acids. Neuropsychopharmacology, 30(2), 223.
[13] Lee op. cit.
[14] Ibid.
[15] Ibid.
[16] Ibid.
[17] Ibid.
[18] Ebner op. cit.
[19] Ibid.
[20] Ibid.
[21] Ibid.
[22] Ibid.
[23] Ibid.
[24] Sippel op. cit.
[25] Ibid.
[26] Ibid.
[27] Ibid.
[28] Ibid.
Clinical Contributor
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Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.
