New oxytocin sensor: novel applications in psychiatry

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A recent study from the University of Lausanne unveils a new method to measure oxytocin in the brain using a bioengineered fluorescent sensor. The applications of this sensor are novel and promising for psychiatry.

Oxytocin

Oxytocin is a neuropeptide produced by the hypothalamus, an area at the base of the brain that regulates many of the body’s physiological processes as well as instinctive brain behaviors. Neurons in the hypothalamus release oxytocin into the bloodstream as a hormone to promote childbirth and lactation. In addition, these neurons release oxytocin into many areas of the brain where oxytocin can regulate, as a neuromodulator, a variety of behaviors such as mating behavior, social cognition and affiliative emotions, maternal care and the formation of stable relationships.

Alteration of oxytocin signaling in the brain could thus be at the origin of cognitive and emotional dysfunctions associated with neurodevelopmental disorders, such as autism spectrum disorders and social behavior disorders, and even neural aging.

Because the time scales of oxytocin-related physiological and pathological phenomena are diverse (from seconds, minutes, hours, and days to potentially much longer periods), the dynamics of oxytocin in the brain can be variable depending on behavioral patterns, types of stimuli, and our physical condition.

The role of oxytocin in psychiatry

In addition to its role as an endogenous neuromodulator, oxytocin has emerged as a potential therapeutic agent for psychiatric disorders, as external administration of oxytocin has been found to enhance positive emotions in humans. Therefore, it was originally thought that external administration of oxytocin, either intranasally or intravenously, would reach the brain and exert therapeutic effects.

However, the potency of external administration of oxytocin is controversial, and a recent study in humans has largely invalidated initial observations of the effects of external administration of oxytocin. Therefore, it remains unclear whether external administration of oxytocin can actually reach the brain via the nasal route and/or across the blood-brain barrier.

The challenges of oxytocin detection for future treatments

In this context, techniques to detect brain oxytocin dynamics are needed. However, currently available methods, such as microdialysis followed by biochemical assays, have limitations, especially in terms of temporal resolution.

Recently, fluorescent sensors composed of a receptor coupled to a fluorescent protein have been developed as promising tools for the real-time detection of neuromodulators such as dopamine, acetylcholine, norepinephrine and adenosine.

Inspired by these strategies, the research team developed a fluorescent sensor for oxytocin. By measuring with the fiber photometric fluorescence technique, it was shown that this new sensor can report a variety of oxytocin dynamics in the mouse and rat brain, including artificially evoked oxytocin signals, endogenous oxytocin responses during natural behaviors, and endogenous oxytocin dynamics modified by chemical and physical perturbations. With these measurements, it will now be possible to study the administration of oxytocin to better treat certain psychiatric disorders.

The study was conducted by Ron Stoop, full professor at the University of Lausanne’s Faculty of Biology and Medicine and head of the Neurobiology of Anxiety and Fear Research Unit at the CHUV’s Center for Psychiatric Neuroscience, in collaboration with a group of researchers from Peking University.