Central oxytocin – its various effects

Central oxytocin (OXT) plays an important role for social activities, friendship, love, and trust. The beneficial effects of manual therapy and mind-body therapy  are mediated via OXT system in the brain. Thus, the physiological role of central OXT is highly associated with the concept of integrative medicine (OXT health; 2011).

In the central nervous system, OXT  is produced in the neurons of the supraoptic nuclei (SON) and paraventricular nuclei (PVN) of the hypothalamus.

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Besides its well-known physiological functions such as uterus contraction and milk ejection, the recent researches indicate that OXT plays an important role in mother-infant bonding, social attachment, trust, self-healing, and mind-body connection. OXT is also linked to health-promoting cardiovascular, metabolic, analgesic, anti-inflammatory and anti-stress effects (Zheng et al. 2010; Gutkowska et al.2012).

It has been suggested that the increase in OXT is related to calmness and relaxed state. Human and animals studies have shown that various stimuli, such as sight, touch, smell, vocalization, food intake, exercise, and social attachment  stimulate OXT release (Uvanas-Moberg et al., 2005).

1. Social connectedness

Unknown-2As humans are social creatures, prosocial behavior is critical for the individual to interact with the environment. Impairment in social behavior is associated with decreased quality of life and psychopathological states.

Hypothalamic-pituitary-adrenal (HPA) axis plays a major role in initiating stress-responses, and hypothalamic OXT reduces the activity of HPA axis. Positive social behavior reduces HPA axis activity, while negative social interactions can have the opposite effect. Social interactions and attachment involve endocrine systems capable of attenuating HPA axis activity and modulating the autonomic nervous system (Carter 1998).

Access to a supportive network reduced the risk of cardiovascular disease. The social support stimulates chronic OXT release, resulting in long term reduction in blood pressure and anti-stress effects through mediating secondary effects (Uvnas-Moberg 1998).

2. Trust

Trust is indispensable in friendship, love, families and Unknownorganizations, and plays a key role in economic exchange and politics. Human beings exhibit substantial interpersonal trust even with strangers. Higher OXT levels are associated with trustworthy behavior. Perceptions of intentions of trust affect levels of circulating OXT (Zak et al., 2005).

Intranasal administration of OXT spray promotes a substantial increase in trusting behavior. OXT specifically affects an individual’s willingness to accept social risks arising through interpersonal interactions. OXT causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions (Kosfeld et al. 2006).

3. Romantic love

images-82Romantic and maternal love are linked to the perpetuation of species and therefore has a closely linked biological function of crucial evolutionary importance (Zeki 2007). Romantic relationships can have a profound effect on human health and well-being. In contrast, the loss of intimate bonds  associate with physical and emotional distress.

Both love and social attachments function to facilitate reproduction, provide a sense of happiness, and reduce anxiety or stress. OXT is released at the nonverbal display of romantic love and thus plays a key role in feelings of love associated with sexual desire and commitment (Gonzaga et al. 2006).

4. Sexual behavior

OXT influences motivation and rewarding aspects of sexual behavior. OXT is released into the circulation during arousal in both men and women with levels peaking during orgasm (Meston et al., 2000). In men, intranasal inhalation of OXT enhanced self-perception of arousal during masturbation (Burri et al., 2008).

5. Anti-stress effects 

When subjected to stress, corticotropin releasing factor (CRF) is secreted from the stress free-2hypothalamus, which results in the secretion of corticosterone (cortisol) from the adrenal cortex to guard against stress disorders.

In response to psychological stressors, there is a dose dependent effect of OXT in attenuating stress-induced HPA axis activation on neural circuits including the PVN. OXT administration significantly attenuated the release of ACTH and cortisol and the increase in CRF mRNA expression in the PVN in response to stress (Windle et al. 2004).

OXT induces a subjective feeling of general well-being through suppression of anxiety, hostility and fear. In human studies, the intranasal OXT administration exhibited increased calmness and decreased anxiety in response to the social stress loading. The anxiolytic (anti-anxiety) effect was greatest in those who had both social support and OXT administration (Heinrichs et al., 2003). Thus, OXT seems to enhance the buffering effect of social support on stress responsiveness.

OXT is a likely candidate for treatment of patients with post-traumatic stress disorders (PTSD) through a reduction of fear response and an increase of social functioning (Olff et al. 2010; Seng et al. 2010).Compassion

For anxiety disorders, patients are often given supportive medications such as selective serotonin reuptake inhibitors (SSRIs) and diazepam (a minor tranquilizer). One of the actions of SSRIs is through increased OXT release. Administration of SSRIs increased plasma OXT levels in rats (Uvnas-Moberg et al., 1999).

The median raphe nucleus is a main site of action for SSRI anti-depressants. OXT infusion facilitated serotonin (5-HT) release within the median raphe nucleus and reduces anxiety-related behavior in mice. Thus, OXT may regulate 5-HT release and exert anxiolytic effects via direct activation of OXT receptor expressed in 5-HT neurons (Yoshida et al. 2009).

Slide11The inhibitory effect of OXT may not directly act on CRF neurons. Gamma-aminobutyric acid (GABA) is the major inhibitory amino acid transmitter in the brain. GABAergic neurons are located in the immediate surroundings of the PVN (peri-PVN. These GABA-projecting neurons into the PVN are known to inhibit CRF expression via GABAA receptors (Cullinan et al., 2008). A recent study suggests that OXT inhibits acute restraint stress-induced CRF mRNA expression via GABAA receptors in the PVN (Bulbul et al. 2011).

It is likely that the anxiolytic affect of OXT is mediated via GABAA receptors at the PVN. The anxiolytic agent, diazepam, is a GABAA receptor agonist (a stimulant of GABAA receptor). Animal studies showed that subcutaneous administration of low dose of OXT has an anxiolytic effect very similar to clinically used diazepam (Uvnas-Moberg et al., 1994).

6. Anti-nociceptive effects

In addition to opioid system, anti-nociceptive effect of images-3somatosensory stimulation is mediated via OXT system (Yang et al., 2007). The descending inhibitory systemalso receives a wide array of afferent modulations from the supra-brainstem regions, including hypothalamus. It has been documented that there is direct descending OXT neuron projection from the PVN to the spinal cord. This is the way by which stimulation of hypothalamic OXT neurons modulates nociceptive responses (Rojas-Piloni et al.2010).

The possible mechanisms of anti-nociceptive effects of hypothalamic OXT are; (1) a direct descending projection of OXTergic neurons from the PVN to spinal cord and modulation of spinal dorsal horn neurons (#1; spinal pathway); (2) a descending projection of OXTergic neurons from the PVN to PAG to enhance opioid (OP) release (#2; ponto-medullary pathway); (3) OXT-induced inhibition on CRF release and reduction of systemic cortisol (#3; CRF-HPA axis pathway).

Slide29Clinical studies showed that intravenous infusion of OXT significantly increases thresholds for visceral perception in IBS patients (Louvel et al., 1996).

7. Cardiovascular effects

heart disOXT has both central and peripheral actions on cardiovascular function. Functional OXT receptors have been discovered in the rat and human heart, as well as in vascular beds (Jankowski et al., 2000).

The cardiovascular activities of OXT include: lowering blood pressure, parasympathetic neuromodulation, vasodilatation,  anti-inflammatory, anti-oxidative, and metabolic effects. These effects are mediated, at least in part, by stimulating cardio-protective mediators, such as nitric oxide (NO) and atrial natriuretic peptide (ANP). OXT has the capacity to generate cardiac myocytes from various types of stem cells (Gutkowska et al.2012).

Daily administration of OXT for 5–14 days reduced blood pressure. Massage-like stroking also caused blood pressure reductions via enhancing endogenous OXT activity (Holst et al. 2002). Enhanced OXT activity leads to inhibition of central and peripheral adrenergic and HPA axis activity, while promoting parasympathetic cardiac control (Mukaddam-Daher et al., 2001).