Brain receptors could affect opioid response

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Mu opioid receptors (MORs) located on certain cells in the brain’s medial habenula may regulate unpleasant, or aversive, effects of opioid use, a National Institute on Drug Abuse-sponsored study recently found.

The medial habenula processes unpleasant experiences while MORs are responsible for behaviors and withdrawal symptoms induced by naloxone, the drug used to reverse an opioid overdose. The medial habenula has the highest density of MORs in the brain.

“This is a very new role for the MOR, classically known as a reward-producing receptor through disinhibition of dopamine neurons at the level of mesolimbic networks,” Dr. Brigitte Kieffer, the study’s senior investigator, said. “Our data show that this receptor would also limit aversion at the level of another brain circuit involving the habenula, suggesting that the MOR is not only ‘pro-reward,’ but also ‘anti-aversion.’”

Researchers from the McGill University Douglas Research Centre genetically altered mice to remove MORs from a subset of neurons that are mainly found in the medial habenula. The mice, along with a control group, were given morphine and/or naloxone.

Mice in both groups had similar reactions to morphine.

The genetically altered mice did not avoid the place where they had received naloxone and showed fewer physical signs of naloxone-induced withdrawal.

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