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Opioid dependence found to permanently change brains of rats:
Approximately one-quarter of patients who are prescribed opioids for chronic pain misuse them, with five to 10 percent developing an opioid use disorder or addiction. In a new study, published Jan. 14, 2020 in PNAS, researchers at University of California San Diego School of Medicine found that opioid dependence produced permanent changes in the brains of rats.
More specifically, researchers reported that dependence on oxycodone, a potent opioid painkiller, led to permanent neuro-adaptations of the central nucleus of the amygdala (CeA) at the level of the nociceptin system, a brainwide network that modulates transmission of pain. Downregulation or suppression of the nociceptin system in the CeA led to an increase in activation of GABA receptors in rats highly addicted to opioids. The discovery is consistent with previous findings reporting CeA neuroa-daptations after cocaine and alcohol dependence.
When researchers restored nociceptin levels in the CeA, it resulted in normalization of GABAergic transmission and a reduction of the rats' opioid consumption.
"This suggests the nociceptin system may be a promising target for the treatment of opioid use disorder," said senior author Giordano de Guglielmo, PharmD, PhD, assistant professor in the Department of Psychiatry at UC San Diego School of Medicine.
"To reveal the role of nociceptin in the central nucleus of the amygdala, we used a multidisciplinary approach with behavioral models, molecular biology and electrophysiology," said first author Marsida Kallupi, PharmD, PhD, assistant professor in the Department of Psychiatry. "That allowed us to conclude that downregulation of this peptide may be partially responsible for excessive opioid addiction-like behaviors."
Marsida Kallupi, Lieselot L. G. Carrette, Jenni Kononoff, Leah C. Solberg Woods, Abraham A. Palmer, Paul Schweitzer, Olivier George, Giordano de Guglielmo. Nociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA–GABA transmission in highly addicted rats. Proceedings of the National Academy of Sciences, 2020; 201915143 DOI: 10.1073/pnas.1915143117
(Score: 0) by Anonymous Coward on Friday January 31 2020, @03:00PM (2 children)
Not at all! This is the whole point. Just because you've observed changes in the brain does not mean you know anything particularly insightful.
Right now our knowledge of the brain, a causal systematic understanding is 0. We currently analyze the brain similar to a person who had no ability to interact with a computer might analyze said computer. They could use a voltmeter, thermometer and other tools to see which areas were active during various scenarios. They could create a lot of correlations, some of them reasonably replicable. Yet I'm sure you'd agree that they'd stand effectively 0 chance of 'cracking' the BIOS with such crude tools, let alone meaningfully debugging malfunctioning programs. And any 'debugging' they did do would be the equivalent of crude solders which seem to have some effect on the target area yet with a practically 0 knowledge of what else they were effecting beyond what was readily apparent. 'Well the computer's still on, so we couldn't have done anything too bad.'
The real risk here is one of false knowledge. Our toolset is expanding quite rapidly beyond just a voltmeter or thermometer, yet we remain what is likely many centuries before we will have any genuine understanding of what we're dealing with. In the past ~4 decades mental illness rates along various psychological disorders have absolutely skyrocketed. Isn't it rather amusing that that it's the exact same time frame upon which a whole new hoard of new drugs and treatments of all sorts have been inflicted upon the population? Of course there's a causality question here. Are all the new drugs emerging because people are losing their shit? Or are people losing their shit because of all the new drugs?
We're so quick to forget that not long ago the state of the art in medicine was drilling holes into people's heads for disorders. This was happening all the way up til the 1960s at all levels of society. One of the most famous lobotomy recipients was Rosemary Kennedy - JFK's sister. Seizures and mood swings? Drill a hole in her head, at age 23. Left her incapacitated and unable to speak for the rest of her 86 year long life. We're a pretty damn stupid species when it comes to treating our illnesses. The arrogance to lead us to believe that such arrogance is now only a thing of the past is the exact same arrogance that led people to trust in drilling holes in their heads.
(Score: 2) by Booga1 on Friday January 31 2020, @10:27PM (1 child)
Many of these things are certainly true. We may still be at the "black box" testing level for the brain, but clearly some chemicals are the equivalent of "flipping a switch." For example, hormones are generally better understood, but we're still finding long term side effects from some of them.
We have a long way to go to understand why some anti-depressants relieve symptoms for some people and worsen it for others with what appear to be identical symptoms. I don't think that means we should all just give up and say "it is forever unknowable." It is called the practice of medicine for a reason. Primitive as it may seem in some fashion, we have to start somewhere. Along the way to reaching understanding of practically anything so complex as the brain it is just as important to have the negative results from tests. It is still progress when we find out what doesn't work.
(Score: 1, Interesting) by Anonymous Coward on Saturday February 01 2020, @05:51PM
In general I do not disagree. You don't learn aerodynamics from zero without trying to mimic a bird, and probably catastrophically failing. The one major point I would emphasize is that it's not the negative results that concern me, it's the positive ones. When trying to fly, there's no real risk of side affects. If you can get enough lift to get off the ground, and you can safely land it - then you now have a workable flying device. When you're talking about the brain things are much more difficult because a failure can look like a success - a repeatable 'success', no less.
As of 2013 [cbsnews.com] about 1 in 6 Americans takes at least one psychiatric drug over the course of a year - 80% of them report longterm usage. That number is up from very near 0 not that long ago. If these drugs have even the slightest of positive effects, we should be seeing an ultra-positive overall effect on the nation in terms of mental health. Yet we seem to be seeing the exact opposite. When you look at things racially the numbers are even more insane. For instance more than 1 in 5 whites in America is on psychiatric drugs. And those numbers have been increasing extremely rapidly.
If it turns out our positive results are myopic, as history shows time and again that they tend to be, then we're metaphorically drilling a hole into the heads of a huge chunk of the entire nation's population.