A Remedy for Stress: Nociceptin

nociceptinThere exists a stress-alleviating network in the brain, called the nociceptin system, according to researchers at The Scripps Research Institute (TSRI) in La Jolla, California.[1] This network is a potential target for therapies that look to treat anxiety disorders and other stress-related conditions.1

Marisa Roberto, an Associate Professor in TSRI’s Addiction Research department, said, “We were able to demonstrate the ability of this nociceptin anti-stress system to prevent and even reverse some of the cellular effects of acute stress in an animal mode.”1

Nociceptin is naturally produced in the brain and is part of a family of peptides that structurally resemble opioid neurotransmitters.1 However, nociceptin does not act like an opioid at all.1 First identified in 1995, nociceptin binds to its own specific receptors, known as NOP receptors, but it does not bind to other opioid receptors.1 Surprisingly, in a mid-1990s study, when scientists injected the peptide into the brains of mice, it didn’t lessen the pain like most opioid peptides do.1 In fact, it made it worse.1 It has a pain-producing effect.1

Studies that followed found that by simultaneously activating the NOP receptor, nociceptin began acting as an anti-opioid.1 It has the ability to affect pain perception and block the rewarding properties of opioids.1 In mice studies, nociceptin acts directly on the amygdala—the part of the brain that controls the basic emotional responses to stress.1 It was found that the nociceptin system operates automatically, as part of a natural stress-alleviating feedback response.1

Now, researchers are focusing on understanding how the anti-stress properties of nociceptin functions.1 Roberto and colleagues focused on the nociceptin system in the central amygdala, using an innovative technique to measure the electrical activity of the stress-sensitive neurons.1

A previous study of Roberto and colleagues’ in 2011 showed that a particular stress peptide that was produced in the amygdala—corticotrophin-releasing factor (CRF)—played an important role in the transition from alcohol use to alcohol dependence.1 According to Roberto, this peptide drives the craving people have for alcohol.1 However, nociceptin was able to prevent and reverse some of the effects of alcohol, also having an anti-stress benefit.1 In fact, it did not matter whether the nociceptin was given before or after the CRF had done its job.1 In both cases, nociceptin had counteracted the CRF.1

Therefore, in their latest study, a set of behavioral experiments showed that injecting nociceptin specifically into a rat’s central amygdala had reduced the anxiety-like behaviors in those rats that were stressed.1 However, there was no effect on the non-stressed rats.1

Roberto said, “Stress exposure leads to an over-activation of the nociceptin/NOP system in the central amygdala, which appears to be an adaptive feedback response, designed to bring the brain back towards normalcy.”1

For future studies, Roberto and colleagues plan to focus on whether the nociceptin/NOP system becomes dysfunctional in chronic stress conditions or not.1 Roberto said, “I suspect that chronic stress incudes changes in the amygdala neurons that can contribute to the development of some anxiety disorders.”1

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