How Are Opioids Really Affecting Our Brains? New Study Reveals Surprising Insights
Given opioids’ profound influence on the world – for better or worse – scientists know surprisingly little about how these drugs actually work. A recent study led by researchers from the University of California Davis describes a new method for observing the nervous system’s real-time response to the activation of its opioid receptors.
By incorporating fluorescing receptors in neurons of mice, the team visualized the activity of opioids inside a living brain. For many, the word ‘opioid’ brings to mind drugs like heroin and fentanyl. However, the human body has its own opioid system, integral to the brain’s reward and aversion pathways.
This system revolves around three receptors: kappa (κOR), delta (δOR), and mu (µOR), activated by various short-chained amino acids released by neurons in response to pleasure, pain, and stress. The best-known of these opioid neuropeptides are probably endorphins – a portmanteau of ‘endogenous morphine’ – but there are many others.
Opioid drugs also bind strongly to and activate our opioid receptors. While there are non-psychoactive opioid drugs – like the anti-diarrheal drug loperamide – most suppress pain and induce strong feelings of euphoria, forcing the brain to adapt to a new opioid baseline. This makes them valuable as painkillers but also highly addictive.
Understanding the complexities of how neuropeptides interact with the opioid system is challenging. As the paper points out, “[The receptors] can be activated by at least 20 endogenous opioid peptides with differential affinity and selectivity.”
“Differential affinity and selectivity” means different opioids bind more strongly or weakly to each receptor, making receptor activation more like a light bulb on a dimmer than a simple on/off switch. The tiny quantities of neuropeptides involved in the opioid system have also proven a hurdle. The paper notes that “the released concentration may also be at orders of magnitude lower than classical neurotransmitters… As a result, it has been exceedingly difficult to study the processes that regulate opioid neuropeptide release.”
There are far more synthetic opioids than neuropeptides, all affecting the brain in subtly different ways. The paper describes a new technique for studying what happens at our opioid receptors when they encounter a binding substance, whether an endogenous neuropeptide or an opioid drug.
The technique involves three carefully tuned molecules called biosensors, one based on each of the κOR, δOR, and µOR receptors. These molecules fluoresce as a substance activates the receptor and fade as the receptor returns to an inactive state. The fluorescence is dose-dependent and is also diminished by opioid blockers like naloxone, which bind strongly to receptors without activating them.
Applied to mice with fluorescent biosensors in their brain’s hippocampus region, the team watched the opioid receptors respond to different drugs and neuropeptides. The findings promise to advance our understanding of the opioid system and benefit the search for potential treatments for anxiety and depression, not to mention the quest for a drug that provides the pain relief of existing opioids without the accompanying potential for addiction.
Source: How Are Opioids Really Affecting Our Brains? New Study Reveals Surprising Insights
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