Researchers have developed a light-activated drug that can selectively induce sleep when the nucleus accumbens region of the brain is exposed to light.

Summary: Researchers at the University of Tsukuba have developed a light-activated drug that induces sleep by targeting the nucleus accumbens region of the brain. This region, which plays a key role in motivational behavior and sleep regulation, can be modulated by adenosine A2A receptors (A2AR). The new drug enhances extracellular adenosine activity and, when activated by light, induces sleep in mice without genetic modification. This innovation overcomes previous challenges with photosensitive drugs and demonstrates the potential for using optochemistry to regulate brain functions selectively.

Key Takeaways:

  • A light-sensitive drug was developed to selectively induce sleep by targeting the nucleus accumbens in the brain.
  • The drug modulates adenosine A2A receptors, crucial for regulating sleep and motivation, without affecting other organs.
  • This research overcomes previous hurdles with photosensitive drugs and highlights optochemistry’s potential for precise brain function regulation.

The nucleus accumbens plays a pivotal role in motivational behavior and sleep regulation, modulated by adenosine A2A receptors (A2AR). Hence, selective A2AR regulation within this brain region could control sleep and motivation. 

However, A2ARs are distributed across various organs, including the heart, posing challenges for precise brain-specific modulation without genetic interventions.

A research team led by professor Dr Michael Lazarus and associate professor Tsuyoshi Saitoh, PhD,  (TRiSTAR Fellow) from the Institute of Medicine and the International Institute for Integrative Sleep Medicine (WPI-IIIS) at the University of Tsukuba delved into optochemistry. 

They aimed to develop a novel light-sensitive drug that enhances extracellular adenosine activity. By administering this drug to mice and selectively irradiating the nucleus accumbens with light, they succeeded in inducing sleep artificially without genetic modification.

Conventional photosensitive drugs have faced hurdles in mammals and other living organisms due to problems such as phototoxicity caused by ultraviolet light, blood-brain barrier permeability, and photoreaction efficiency. 

The newly developed photosensitive drug overcomes these issues, showcasing optochemistry’s potential in developing drugs targeting A2AR in the brain and regulating brain function by targeting other central drug receptors.

The study was published in Nature Communications.

DID YOU KNOW: Adenosine A2A receptors (A2AR) in the nucleus accumbens of the brain play an important role in regulating sleep and motivation, but until now, no drugs have been able to selectively modulate their function without affecting other organs or brain areas. In this study, a light-activated allosteric modulator of A2AR was developed and successfully used to remotely induce sleep by selective light irradiation of the nucleus accumbens in mice.

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