Addiction Drug Use Neurotransmitter Orexin and Reward Seeking in the Brain Orexin Could Be Key to New Drug Treatments By Buddy T Buddy T Facebook Twitter Buddy T is an anonymous writer and founding member of the Online Al-Anon Outreach Committee with decades of experience writing about alcoholism. Learn about our editorial process Updated on February 24, 2021 Medically reviewed Verywell Mind articles are reviewed by board-certified physicians and mental healthcare professionals. Medical Reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more. by Huma Sheikh, MD Medically reviewed by Huma Sheikh, MD Facebook LinkedIn Twitter Huma Sheikh, MD, is a board-certified neurologist, specializing in migraine and stroke, and affiliated with Mount Sinai of New York. Learn about our Medical Review Board Print Getty Images Orexin, also known as hypocretin, is a neurotransmitter discovered in 1998 which is produced in the hypothalamus region of the brain that is involved in wakefulness and arousal. Because of its role related to sleep, orexin has been targeted as a treatment for sleep disorders. Medications known as "orexin receptor antagonists" have been developed to block the signaling of the chemical in the brain to promote sleep. Because orexin plays a role in keeping us awake and alert, blocking its effects could potentially improve sleep. The U.S. Food and Drug Administration has approved suborexant (Belsomra), an orexin receptor antagonist, as a sleeping aid. Scientists have found that orexin may also play a role in reward-seeking, drug relapse, and addiction and therefore may lead to new treatments for drug addiction. Researchers found that orexin neurons extend into the regions of the brain linked to reward pathways suggesting that these transmitters may play a role in motivation and reward-seeking behavior. Penn State researcher Glenda Harris, Ph.D., working with Gary Aston-Jones, Ph.D., in the Department of Psychiatry, investigated the relationship between orexin and reward-seeking by studying orexin function in rats using a behavioral test aimed at mimicking food- and drug-reward seeking and drug relapse. "The lateral hypothalamus has been tied to reward and pleasure for decades, but the specific circuits and chemicals involved have been elusive," says Aston-Jones. "This is the first indication that the neuropeptide orexin is a critical element in reward-seeking and drug addiction. These results provide a novel and specific target for developing new approaches to treat addiction, obesity, and other disorders associated with dysfunctional reward processing." The researchers found a strong link between the activation of orexin neurons in the lateral hypothalamus and reward-seeking of morphine, cocaine, and food. They found that the highest levels of activity in the orexin neurons appeared in rats demonstrating the greatest level of reward-seeking. Turning Drug Seeking on and Off The study revealed an association between orexins and the reward pathways of the lab rats in three ways: Activation of orexin neurons is related to preferences by the rats for cues associated with drug and food rewardsChemical activation of orexin neurons reinstated an extinguished drug-seeking behaviorDirect injection of orexin reinstated drug-seeking behavior. In addition, when the researchers gave the rats a specific orexin antagonist, the animals' initial learning of a drug preference and the reinstatement of extinguished drug-seeking behavior were blocked. Reward-Seeking Can Be Extinguished "Because of the relationship between orexin activation and reinstatement of reward-seeking behavior, these findings may have implications for understanding drug-taking relapse in humans," the researchers wrote. "An animal's reward-seeking can be extinguished over time by repeatedly exposing the animal to the environment possessing drug-related cues without the previous drug rewards." "After extinguishing reward-seeking, presenting a stimulus that was previously associated with the drug will lead animals to quickly resume reward-seeking, similar to what happens when humans have a drug relapse," they said. New Target for Developing Treatment Using a neuropeptide that activates orexin neurons in the lateral hypothalamus, Harris, and colleagues were able to reinstate drug-seeking in the rats whose drug-seeking behavior was previously extinguished. "These findings indicate a new set of neurons and associated neuronal receptors that are critical in consummatory reward processing," says Aston-Jones. "This provides a new target for developing drugs to treat disorders of reward processing such as drug and alcohol addiction, smoking, and obesity." Sources Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Ebrahim, IO, et al. "The hypocretin/orexin system." Journal of the Royal Society of Medicine May 2002 Harris, GC et al. "A Role for Lateral Hypothalamic Orexin Neurons in Reward Seeking." Nature September 22, 2005 National Sleep Foundation. "Orexin Receptor Antagonists: A New Class of Sleeping Pill." 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