Biology

Beyond Dopamine: New Brain Reward Circuitry Discovered

Brain Reward Circuitry Concept

The process of better understanding the brain is like building a puzzle whose pieces grow in number over time.

In a paper published in Nature Neuroscience, researchers pushed the science forward on our reward pathways.

The key to overcoming addictions and psychiatric disorders lives deep inside the netherworld of our brains and the circuitry that causes us to feel good. Just like space, this region of the brain needs more exploration.

The oldest and most known reward pathway is the mesolimbic dopamine system, which is composed of neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens — a key structure in mediating emotional and motivation processing,

Dopamine is a neurotransmitter that is released when the brain is expecting reward. A spike in dopamine could come be from eating pizza, dancing, shopping and sex. But it can also come from drugs, and lead to substance abuse.

In the search for new therapies to treat addiction and psychiatric illness, researchers are examining pathways beyond dopamine that could play a role in reward and reinforcement.

In a paper published in Nature Neuroscience, researchers from the Bruchas Lab at UW Medicine pushed the science forward on our reward pathways and found another such pathway.

“This study opens new avenues to understanding reward circuitry that might be altered in abuse of nicotine, opiates or other drugs as well as neuropsychiatric diseases that affect reward processing including depression,” said corresponding author Dr. Michael Bruchas, professor of anesthesiology and pain medicine at the University of Washington School of Medicine.

The researchers found that approximately 30% of cells in the VTA – the midbrain – are GABA neurons. Neurons are the fundamental units of the brain and nervous system, the cells responsible for receiving sensory input from the external world, for sending motor commands to our muscles, and for transforming and relaying the electrical signals at every step in between.

VTA GABA neurons have increasingly been recognized as involved in reward and aversion, as well as potential targets for the treatment of addiction, depression and other stress-linked disorders.

“What we found are unique GABAergic cells that project broadly to the nucleus accumbens, but projections only to a specific portion contribute to reward reinforcement,” said co-lead author Raajaram Gowrishankar, a postdoctoral scholar in the Bruchas Lab and the Center for the Neurobiology of Addiction, Pain and Emotion.

In male and female mice, researchers showed that long-range GABA neurons from the VTA to the ventral, but not the dorsal, nucleus accumben shell are engaged in reward and reinforcement behavior. They showed that this GABAergic projection inhibit cholinergic interneurons – key players in reward-related learning.

These findings “further our understanding of neuronal circuits that are directly implicated in neuropsychiatric conditions such as depression and addiction,” the researchers wrote.

Gowrishankar said the findings are allowing scientists to understand subregions of the brain and to visualize how specific neuromodulators are released during reward processing. In science terms, the researchers were able to highlight heterogeneity, or differences, in the brain.

“It’s really important that we don’t think of structures in the brain as monolithic,” said Gowrishankar. “There’s lots of little nuance in brain – how plastic it is, how it’s wired. This finding is showing one way how differences can play out.”

Reference: “Ventral tegmental area GABAergic inhibition of cholinergic interneurons in the ventral nucleus accumbens shell promotes reward reinforcement” by Ream Al-Hasani, Raajaram Gowrishankar, Gavin P. Schmitz, Christian E. Pedersen, David J. Marcus, Sofia E. Shirley, Taylor E. Hobbs, Abigail J. Elerding, Sophie J. Renaud, Miao Jing, Yulong Li, Veronica A. Alvarez, Julia C. Lemos and Michael R. Bruchas, 12 August 2021, Nature Neuroscience.
DOI: 10.1038/s41593-021-00898-2

This research was funded by grants R00 DA038725, F31 DA051124, R37 DA033396, P30 DA048736 from the National Institutes of Health and National Institute on Drug Abuse.

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  • I was just reading a very interesting article about neuroscience i.e. dopamine and it really caught my attention because i have been on green liquid methadone for quite sometime now and if i had known the side effects back then i would never of touched it,i would of just went threw the 5 horrible withdrawl days that you go threw with heroin,but now if i want to go off methadone cold turkey like i did before with heroin i cannot because it takes much much longer,first of all you are advised to come down a little at a time yet you stil have the side effects and the worst one is the sweating i mean you can walk around for lets say 2 minutes to the shop and 2 minutes back home and as you walk in the door your whole body is covered in sweat it affects upto nearly 50% of people but i know without a doubt that statistic is much higher plus you sweat something like 5 times more than the average person anyway when you are finally down to a low dose and decide to stop taking it and going cold turkey for the rest to leave your body it doesnt stop after 5 days like herion does it can last upto 7 weeks and in some cases you might not feel completely normal for up to at least 6-months so you are just swapping one drug for another and even tho methadone saves lives it is a nightmare in the long run for if I were able to make my brain just give me the dopamine with out actually having to take the drug then that would be a true miracle for me and a lot more people like me anyway I just said I would leave this comment and maybe orders out there might feel the way I do thank you very much for reading my comment.

    • From someone who was once addicted to methadone, I agree. I got addicted to prescription pain medication after having multiple surgeries due to severe bouts of diverticulitis from 2006 to 2009. Believe it or not but my insurance actually sent me to a methadone clinic as treatment for my Oxycodone addiction. It took me three and a half years before I realized I was WAY MORE addicted to the methadone than I was the oxycodones. The methadone literally became my master and the clinic my church. I finally said enough is enough and did a rapid taper from the highest legal dose to nothing within a ten day period. It seriously took me YEARS—like almost four of em—to recovery from it. It scarred me and f###ed my brain up so bad that I doubt I’ll ever be the same as I once was. I’ve been clean now for over four years and I still feel emotionally wounded. The silver lining however is: A) I no longer feel like a slave to a drug, and B) I now feel all of life’s highs and lows at an intensity I had never known before. Please do not let my story—my experience—deter you or anyone else from trying to quit. Believe me, if someone as unheroic as me did it, you can do it too. It will be hard but it will be worth it. One thing I’d highly recommend to you out of my own hindsight is to find a support group to help you through the process. I feel that would’ve helped me stupendously. I promise you, the journey within is a trip worth taking. You may even find that it opens a doorway for you to self-actualization.

  • I agree in the long run Methadone is far worse to come off of. They don't tell you all the side effects either like it kills testosterone in your body which causes a number of other problems and that's just 1 side effect. In my opinion it would probably be healthier if they did heroin maintenance like in some European countries. I came off Methadone and didn't feel right for almost a year and the 1st 3 months are a living hell!! In all honesty I'd rather come off pills or heroin 5x before Methadone 1 time.

  • I have been on diagnosis of depression for 15years ago which I use to take arteen and some drugs,but now i am on cloxapine for the past one year I hope condition will get much more better so I will able to cope with marriage and family affairs and also take work to be of high compassionate, now I manage my sister's company which she presides payment of my drugs,housing, clothing, feeding and monthly salary. I hope the dosage will take care of my health situations

  • From someone who was once addicted to methadone, I agree with what both Patrick and Shane said. I got addicted to prescription pain medication after having multiple surgeries due to severe bouts of diverticulitis from 2006 to 2009. Believe it or not but my insurance actually sent me to a methadone clinic as treatment for my Oxycodone addiction. It took me three and a half years before I realized I was WAY MORE addicted to the methadone than I was the oxycodones. The methadone literally became my master and the clinic my church. I finally said enough is enough and did a rapid taper from the highest legal dose to nothing within a ten day period. It seriously took me YEARS—like almost four of em—to recovery from it. It scarred me and f###ed my brain up so bad that I doubt I’ll ever be the same as I once was. I’ve been clean now for over four years and I still feel emotionally wounded. The silver lining however is: A) I no longer feel like a slave to a drug, and B) I now feel all of life’s highs and lows at an intensity I had never known before. Please do not let my story—my experience—deter either one of you or anyone else from trying to quit. Believe me, if I can, anyone can. I promise you, the journey within is a trip worth taking. You may even find that it opens a doorway for you to self-actualization.

  • To those suffering from addiction, depression, anxiety and insomnia I highly highly suggest checking out Fisher Wallace Stimulator. It’s been life changing for me to say the least.

By
UW Medicine

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