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Psychiatric Times. Vol. 25 No. 9
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Molecules of the Mind 

Oxytocin and the Bottom Line

By John J. Medina, PhD

| August 1, 2008
Dr Medina is a developmental molecular biologist and private consultant, with research interests in the genetics of psychiatric disorders.

Trust can be a scary proposition. Among other characteristics, trusting someone involves the ability to measurably predict a behavior on the basis of nothing more than a memory, an impression, or a whim. For creatures like us, who spend a ridiculous amount of time with unpredictable strangers, brokering trust is an oddly important survival strategy.

Trusting behaviors have fascinated a broad swath of the behavioral research community, from social scientists and evolutionary theorists to cellular and molecular biologists. This community has, over the past few years, acquired insight from unlikely corners of academia, including, of all places, business schools. This month’s column is all about an interesting collision between biologists, economists, and the human capacity to rely on the character or integrity of other people.

Those of you who are already familiar with the topic know I am about to discuss one of biology’s most ancient neurotransmitters: oxytocin(Drug information on oxytocin). Its molecular mechanisms have become increasingly well characterized and have strong links to behaviors that involve the seemingly subjective experience of trust. Oxytocin has even been hypothesized to influence economic decisions. Can it?


The purpose of this column is to answer that question. I will start with the basic biology of this small molecule, briefly discuss its multifaceted role in animal behavior, and then move to data involving human subjects and their monetary decisions. As you shall see, it is not at all far-fetched to include economists as important peers in the greater neurobiological community. We may just need to trust them a little more.

Oxytocin Basics

Oxytocin was famously isolated more than half a century ago. Its identification and subsequent characterization earned Vincent du Vigneaud a Nobel Prize in chemistry in 1955.

That discovery turned out to be the easy part. Over the years, oxytocin has proved to be maddeningly difficult to work with for several reasons. Oxytocin is not a big, bulky protein but a little peptide weighing in at a paltry 1007 daltons (9 amino acids). It is produced in minute quantities in the human brain and degrades soon after manufacture (an effective half-life of less than 180 seconds).

Although it is tricky to work with, great strides have been made in understanding its biology. In the brain, oxytocin functions as a neurotransmitter, exerting its effects through a complex of interconnecting neural pathways. Oxytocinergic neurons display widespread projections throughout the CNS. In these cells, the peptide functions by binding to the oxytocin receptor, which is a fairly nondescript class I G protein–coupled receptor linked to phospholipase C. Specific brain nuclei that are mostly involved in emotional regulation possess dense fields of these receptors, mediating many of oxytocin’s behavioral effects. These regions include the septum, hypothalamus, brain stem, and amygdaloid complex.

Oxytocin can also enter non-CNS tissue, functioning not like a neurotransmitter but like a hormone. Suckling, stress, and parturition all can stimulate oxytocin release from the posterior pituitary into peripheral circulation. Predictably, oxytocin receptors exist in many regions of the body outside the CNS, including in the uterus and breast. The peptide is involved in the dilation of the cervix before birth and can cause uterine contractions in the terminal stages of labor. It is also involved in the so-called letdown reflex in lactation, causing milk to gather into the breast’s collecting chambers.

Oxytocin also has effects on some truly complex animal behaviors. In female rats, the administration of oxytocin antagonists after they give birth eradicates the animals’ maternal behaviors. Virgin female sheep begin to exhibit maternal behavior toward unrelated lambs when oxytocin is exogenously supplied to their cerebrospinal fluid. Oxytocin in prairie voles helps to maintain monogamous pair-bonding behavior when released into the brain of females during periods of sexual activity. These are not unusual findings. Oxytocin mediates bonding social behaviors in a wide variety of species. In humans, oxytocin appears to assist in the formation and maintenance of sexual arousal.

The breadth of oxytocin-mediated behaviors has caught the attention of researchers who are interested in human social interactions—including trust. To talk about the effects of oxytocin on trust-associated behaviors, I turn to the work of Paul Zak, Ernst Fehr, and their colleagues, who have created experimental paradigms (games, actually) in which the seemingly subjective experience of trust competency can be reliably measured. I discuss the design of one of these games and the interesting role oxytocin plays in it next.

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