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Discovery of morphine regulating protein may help reduce addiction

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Posted September 24, 2015

Morphine is a very well-known pain medication of the opiate type. It has high addiction liability and acts directly on the central nervous system, decreasing the feeling of pain. There were many stories about opiates throughout the history and morphine is not an exception – once in the 18th century it was used as currency to reverse the trade imbalance between China and Britain. Morphine‘s characteristics were misunderstood ever since – although it was widely used (and misused) scientists only now begin to understand how it actually works.

Morphine throughout the history since its discovery was widely used as a pain medicine. This is an ampule of morphine meant to be used during WW2 by a soldier if in need. However, it has a high addiction liability and not everything is known about how it works. Image credit: Gaius Cornelius via Wikimedia, CC BY-SA 3.0

Morphine throughout the history since its discovery was widely used as a pain medicine. This is an ampule of morphine meant to be used during WW2 by a soldier if in need. However, it has a high addiction liability and not everything is known about how it works. Image credit: Gaius Cornelius via Wikimedia, CC BY-SA 3.0

Morphine works by affecting a specific protein that has been part of vertebrate anatomy for nearly a half-billion years. Despite such a substantial time period, science never well understood the regulation of these receptor proteins. Now team of researchers at The Scripps Research Institute have demonstrated that a specific molecule controls morphine receptor signalling in a small group of brain cells.

Findings of this research will have two important implications – scientists will have more knowledge needed to develop pain medications with lower addiction liability and maybe they can create therapies that work as genetic predisposition of patients to addiction before treatment.

This molecule that controls morphine receptor signalling is known as a regulator of G protein signalling protein, which controls the morphine receptor (mu opioid receptor). This is a rather complicated scheme and scientists only got to understand it using genetically modified animal models lacking a particular RGS protein called RGS7, which is abundant in the brain.

The research demonstrated that eliminating the protein enhanced reward, increased pain relief, delayed tolerance and heightened withdrawal in response to self-administered morphine doses. In short, eliminating the protein made animal models predisposed to morphine addiction.

Professor Kirill Martemyanov, leader of the research team, said: “the mu opioid receptor acts as a conductor of the drug’s effects, while RGS7 acts as a brake on the signal. The animals could press a lever to receive an infusion of morphine. We looked at the number of lever presses to determine how much they liked it and, judging from this test, mice lacking RGS7 craved the drug much more than their normal siblings”.

Researchers found that RGS7 protein exerts its effects by regulating morphine-induced changes in excitability of neurons and plasticity of synapses—the ability of the synapse, the junction between two nerve cells, to change its function. In other words, study uncovered how RGS7 protein could be targeted with innovative drug therapies. New medicine could potentially target the RGS7 protein and reduce some of the detrimental side-effects of opiates.

Scientists say that findings open many new diagnostic features as well. Such as individual dosage of opioids could be selected, if patients would be tested before treatment. Simple blood test would actually be enough as patients would be tested for RGS7 levels – patients with a deficient copy of the RGS7 gene might need much lower doses of opioids. These findings also provide some explanation why some people have more trouble with addictions than others.

Unexpectedly, animal models which were used in the research and had craving for drug, because of lack of RGS7 protein, put more efforts into obtaining food too. This also suggests that this particular protein may be a more general regulator of reward behaviour, which extends beyond drug-induced euphoria. Scientists hypothesized this way before, but craving for food besides craving for drug further supports this idea.

These findings shed new light on the pain medicine that has been used for centuries. When used with caution and with care of the doctor, morphine is a very useful drug, easing the suffering of patients. However, people used and abused opiates since their discovery. Therefore, researches like this help to understand the mechanisms how these drugs work and how negative effects can be kept to a minimum.

Source: Scripps

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