Opioids: Probing the Mechanism for Addiction, Analgesic Relief, and Tolerance

A preclinical study published online February 24 in the journal Neuropsychopharmacology is the first to show that the effect of opioids on the activity of a protein, RGS9-2, in the reward center of the brain alters the threshold for pain relief and affects opioid tolerance. The research could provide valuable insight to promote the development of new treatments for addiction, as well as more effective and less dangerous analgesics.

In the study, targeting mouse nucleus accumbens, a key component of the brain’s reward center, investigators used a novel technique known as optogenetics, which allows the activation of specific neurons via blue light in real time, to determine the exact cell types of the brain reward center responsible for the reduced analgesic response. Researchers found that by inactivating RGS9-2, they could effect a tenfold increase in sensitivity to the rewarding actions of morphine, severe morphine dependence, a better analgesic response, and delayed development of tolerance. While opiate analgesics act in several brain regions to alleviate pain, their actions in the brain reward center may also affect analgesia. The nucleus accumbens may also affect the development of morphine tolerance, via mechanism that are distinct from those described in other regions of the brain.

A news story on the research may be read here.

The journal abstract, with link to the full article, may be read here.

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