Oxytocin Peptide: Social Bonding and Behavioral Studies

Oxytocin is a cyclic nonapeptide hormone having the amino acid sequence CYIQNCPLG. It also serves as a neurotransmitter in the brain and is the main hormone responsible for uterine contractions and milk ejection in the posterior pituitary. It is thought to have an effect on social cognition and behavior when combined with the neuropeptide vasopressin. It functions as both an oxytocic and a vasodilator agent. It is a heterodetic cyclic peptide and a neuropeptide hormone.

Oxytocin is a neuropeptide that is most well-known for its functions in childbirth (uterine contractions) and lactation (milk ejection). However, it also plays an important role in social bonding, trust, and different aspects of sexual behavior. It acts as a chemical messenger in the brain and influences complex social interactions by modulating sentiments and cognitive functions such as memory and recognition. For this reason, it is often referred to as the "love hormone." 

Mechanism of Action of Oxytocin Peptide

Oxytocin binds to certain G protein-coupled receptors (GPCRs) on target cells, primarily the oxytocin receptor (OTR). This binding causes a signaling cascade that results in higher amounts of calcium inside the cell. This causes the muscles in the uterus to contract during birthing and causes the mammary glands to discharge milk during breastfeeding.

Oxytocin is also important for social behaviors because it changes brain activity by activating similar receptors in the central nervous system. [2] The effect of oxytocin on the brain is that it interacts with OTRs in certain areas to influence social behaviors such as bonding, trust, and recognition.

Research Evidence of Oxytocin

Oxytocin has been found to play a role in a number of areas, including intimacy, social recognition, pair bonding, and anxiety, according to a large number of studies. Oxytocin is known for its peripheral involvement in childbirth and breastfeeding, but it also has a central role in the brain, where it helps to control behavior.

In another experiment that was conducted on human subjects, positron emission tomography was utilized to assess the effects of exogenous oxytocin injection as a modulator on the neurotransmission of serotonin in patients with autism spectrum disorder to the effects in control patients. The healthy subjects were the only ones who showed a modulatory impact of oxytocin on serotonin.

After oxytocin was administered, there were no alterations in serotoninergic transmission in patients with autism. These findings further support the idea that oxytocin has a modulatory effect on serotonin and that it is involved in autism spectrum disorders [3].

In a similar vein, rats that were administered a serotonergic agonist (5-methoxytryptamine) exhibited a drop in oxytocin in the paraventricular nucleus of the hypothalamus, an increase in serotonin plasma levels, and behavior that resembles autism [4]. This suggests that there is a bilateral connection between oxytocin and serotonin. Mice of both sexes that have an excess of serotonin also have fewer oxytocin-producing cells in their paraventricular nucleus of the hypothalamus.

However, only female mice seem to be able to self-regulate serotonin receptors to excessive systemic serotonin in a way that promotes the survival and functional efficiency of oxytocin cells [5].

Dolen et al. carried out a study to see whether mice preferred a certain place that was associated with social interaction or a room that had previously been associated with social isolation. This activity evaluates the positive effects of social contacts.

The research found that eliminating presynaptic oxytocin receptors in the projection from the dorsal raphe nucleus to the nucleus accumbens is sufficient to eliminate this preference. They did an additional study that showed oxytocin operates by increasing the release of serotonin from the dorsal raphe nucleus projection to the nucleus accumbens. Furthermore, serotonin interacts with 5-HT1B receptors in the accumbens nucleus, which leads to the long-term melancholy of excitatory synapses [6].

Research Applications with Oxytocin

While oxytocin's impact on how social inputs are processed is intriguing, the only way to determine its function in the social brain is through real-life social interactions. These interactions can change the neurohormonal (stress hormone) axis because of the complex nature of the social brain. These changes can have a significant impact on human health and development throughout a person's life.

A groundbreaking study that looked at these connections put 37 healthy males under stress by giving them an evaluative social performance test (the Trier Social Stress Test) after they had received either intranasal oxytocin or a placebo, as well as either social support from a close friend or no social support at all. Each active intervention—oxytocin and social support—independently reduced the increase in cortisol that occurred after a stressful event and induced an increase in calmness ratings after a task. The combination of oxytocin and social support had an additive effect. [7]

It is important to point out that there was a trend toward decreased state anxiety in both the oxytocin–social support group and the oxytocinalone group. Going a step further with these findings, Ditzen and colleagues121 conducted a recent study that is the most naturalistic examination of oxytocin to date.

The study was gender-balanced. In this experiment, 47 heterosexual couples were given either intranasal oxytocin or a placebo before they participated in a filmed talk about a disagreement. Plasma oxytocin had a considerable impact on the levels of cortisol after a stressor, as well as the ratio of positive to negative social behavior that was judged by observers throughout the conversation.

This ratio is an important indicator of successful long-term relationship results. It is also important to highlight that these effects were shown to occur in both men and women, especially considering the gender bias present in existing human oxytocin studies. [8]

Since the 1960s, the effects of oxytocin on memory have been documented in animals, and since the 1980s, they have been documented in humans. Research on animals shows that oxytocin has different impacts on memory depending on a variety of parameters, such as the timing of distribution, social environment, gender, and dosage. Oxytocin levels play a role in memory acquisition and hippocampus-dependent spatial memory in rodents.

It is also necessary for social recognition and partner preference, which are two behavioral representations of social memory. Recent studies on voles have shown that differences in social attachment are linked to changes in the density of oxytocin receptors in the nucleus accumbens.

Additionally, oxytocin "knockout" mice, which are mice that do not have a functional oxytocin system, are unable to recognize other mice of the same species. However, this ability is restored when they are treated with oxytocin. Oxytocin has also been shown to have amnesic effects in animals. It reduces conditioned avoidance, a taught fear memory, which leads to decreased avoidance.

The early human experiments that investigated the effects of oxytocin on memory primarily used linguistic tasks, which raised questions about its ecological application in relation to social memory. These early investigations had inconsistent results. Some studies reported memory impairment, particularly in verbal memory and initial storage rate, while others reported no effect.

This led to lukewarm early appraisals of oxytocin's specific memory effects in humans. The initial studies on oxytocin's role in memory concentrated on its overall impact on arousal. In one study, patients ranked a subjective criterion known as "vigor" lower. More recent tests that used verbal-memory tasks have similarly shown inconsistent results: Oxytocin pretreatment had different impacts on memory. It caused amnesia for terms that had to do with reproduction, while it improved recall for words that described good traits. [9]

Future Research Perspectives On the Use of Oxytocin

In order to create a strong foundation for future treatment options, further research is needed to explore the various roles that oxytocin treatment plays in the field of psychiatry. The role of Oxytocin may be used in a variety of therapeutic ways, which is extremely important for preventing, managing, and maintaining mental health. In order to properly understand the interactions between peptides (including oxytocin and vasopressin), future studies will need to include other key molecules. For instance, endogenous opioids, dopamine, corticotropin-releasing hormone, and serotonin

References

1. https://pubchem.ncbi.nlm.nih.gov/compound/Oxytocin#section=Structures

2. https://go.drugbank.com/drugs/DB00107.

3. Lefevre A., Mottolese R., Redouté J., Costes N., Le Bars D., Geoffray M.-M., Leboyer M., Sirigu A. Oxytocin Fails to Recruit Serotonergic Neurotransmission in the Autistic Brain. Cereb. Cortex. 2017;28:4169–4178. doi: 10.1093/cercor/bhx272

4. Madden A.M., Zup S.L. Effects of developmental hyperserotonemia on juvenile play behavior, oxytocin and serotonin re-ceptor expression in the hypothalamus are age and sex dependent. Physiol. Behav. 2014;128:260–269. doi: 10.1016/j.physbeh.2014.01.036

5. Edwards K.A., Madden A.M., Zup S.L. Serotonin receptor regulation as a potential mechanism for sexually dimorphic oxytocin dysregulation in a model of Autism. Brain Res. 2018;1701:85–92. doi: 10.1016/j.brainres.2018.07.020

6. Dolen G., Darvishzadeh A., Huang K.W., Malenka R.C. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature. 2013;501:179–184. doi: 10.1038/nature12518

7. Di Simplicio M, Massey-Chase R, Cowen P, Harmer C. Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers. J Psychopharmacol 2009;23:241–8

8. Ditzen B, Schaer M, Gabriel B, Bodenmann G, Ehlert U, Heinrichs M. Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biol Psychiatry 200;65:728–31.

9. Macdonald, Kai & Macdonald, Tina. (2010). Macdonald K, Macdonald TM. The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans. Harv Rev Psychiatry 18: 1-21. Harvard review of psychiatry. 18. 1-21. 10.3109/10673220903523615.