UCSD researchers find opioid dependence permanently changes brains of rats
Published - 02/08/20 - 09:00 AM | 3615 views | 11 11 comments | 38 38 recommendations | email to a friend | print

Approximately one-quarter of patients who are prescribed opioids for chronic pain misuse them, with 5-10% developing an opioid use disorder or addiction. In a new study, published on Jan. 14, 2020 in PNAS, researchers at the 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 brain-wide network that modulates the 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 neuro-adaptations 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, Ph.D., 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, Ph.D., 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.”

Currently, opioid maintenance therapy is the first-line treatment for opioid dependence, which involves using alternative, less damaging medications, such as methadone, buprenorphine, and naltrexone. These three drugs are the only treatments approved by the U.S. Food and Drug Administration, but all have limitations, either because they act against different receptors, pose safety concerns or are less effective due to the need for strict adherence to treatment. 

Both methadone and buprenorphine target mu-opioid receptors in the brain. The new research builds upon past behavioral and neurochemical studies suggesting the nociceptin system and its receptors (NOP) are also involved in opioid tolerance and reward, addiction to multiple drugs and modulation of stress. Interestingly, while the research demonstrates that NOP is implicated in the development of opioid dependence, it conversely blocks the effects of morphine-based opioids.   

De Guglielmo said several efforts are already underway testing small molecule drugs that target the nociception system, and have produced positive effects in reducing alcohol-seeking behaviors and biology in rats. The new findings indicate they may offer similar potential therapeutic benefit for opioid addiction.

Every day, according to the National Institute on Drug Abuse, more than 130 people in the United States die after overdosing on opioids. Two out of three drug overdose deaths involve an opioid. From 1999 to 2017, the last year for which data is available, almost 400,000 Americans lost their lives to opioids, with 47,600 fatal overdoses in 2017 alone. It’s estimated 2.1 million Americans have an opioid use disorder.

For the full study, visit https://www.pnas.org/content/early/2020/01/10/1915143117.

Comments-icon Post a Comment
mofoso fisto
June 11, 2020
My first symptoms of ALS occurred in 2011, but was diagnosed in 2013. I had severe symptoms ranging from shortness of breath, balance problems, couldn't walk without a walker or a power chair, i had difficulty swallowing and fatigue. I was given medications which helped but only for a short burst of time, then i decided to try alternative measures and began on ALS Formula treatment from Akanni herbal centre , It has made a tremendous difference for me (Visit www. akanniherbalcentre .com). I had improved walking balance, increased appetite, muscle strength, improved eyesight and others. 
June 07, 2020
I was cured of HIV with the used of natural herbs,  I love herbs so much. Most times, injection and drugs are just a waste of time. I was cured 8months ago, i suffered from HIV for 13yrs but with the help of Dr.iniboku herbal medicine, i was cured within few weeks of drinking the herbs he sent to me through courier delivery service. This same doctor also cured my Aunty from herpes, as soon as i heard she had herpes, i quickly refer her to Dr. iniboku and she was cured too after drinking his herbs.I have referred more than 15 persons to Dr.iniboku and they were all cured from their various illness. Have you taken herbs before?. You have spent so much money on drugs,injections,surgeries etc and yet you have no good result to show for it. Contact Dr.iniboku now, he is a herbalist doctor, i assured you of a cure if you drink his natural herbs. Dr.iniboku have herbs that cures Hiv, Herpes, diabetics, asthma, hepatitis, HBP, STD, cancer, chronic, etc. Contact Dr iniboku through his Email address on: [email protected] or WHATSAP/CALL him on 2347059186346 . Please share the good news to other people once you are cured.  
May 23, 2020
HOW I GOT CURED FROM HERPES VIRUS hello I'm from USA , I have been suffering from HERPES virus for the past 3 years and i had constant pain especially in my knees, During the first year I had faith in God that i will be healed someday, but this disease started circulate all over my body and i have been taking treatment from my doctor, few weeks ago i came in search on the internet if i could get any information concerning the prevention of this disease, on my search i saw a testimony of so many people who has been healed from HEPATITIS B, HIV/AID, MRSA DIABETES,HSV, ALS HPV. LEUKAEMIA,ECZEMA,PSORIASIS, and Cancer by this Man called Dr, Ekpen, and he also gave the email address of this man and advice we should contact him for any sickness that he would be of help, so i wrote to Dr. Ekpen telling him about my HERPES Virus he told me not to worry that i will be cured from this deadly disease i never believed it, well after all the procedures and remedy given to me by this man, few weeks later i started experiencing changes all over me as the Doctor assured me that i will be cured,after some time i went to my medical doctor to confirmed if i have be finally cured behold it was true,and now i'm cure totally with Dr.Ekpen medication, So friends my advise is if you have such sickness or any other at all you can email Dr,Ekpen on this email; [email protected] or add him up on what-app 2349021966938 .for assistance. he will help you also , for more information you can also contact me through this email; [email protected]    
mofana fistos
April 07, 2020
My first symptoms of ALS occurred in 2011, but was diagnosed in 2013. I had severe symptoms ranging from shortness of breath, balance problems, couldn't walk without a walker or a power chair, i had difficulty swallowing and fatigue. I was given medications which helped but only for a short burst of time, then i decided to try alternative measures and began on ALS Formula treatment from Akanni herbal centre , It has made a tremendous difference for me (Visit www. akanniherbalcentre .com). I had improved walking balance, increased appetite, muscle strength, improved eyesight and others. 

Jennifer Kelvin
April 07, 2020
The Great Dr.UCHEGBU herbal medicine is a good or perfect cure remedy for HIV Virus, I was diagnose of HIV for almost 4 years, everyday i am always on research looking for a perfect way to get rid of this terrible disease as i always knew that what we need for our health is right here on earth though the scientist say there is know cure for this disease,on my search I saw some different testimony on how Dr. UCHEGBU has been able to cure HIV with is herbal medicine. I decided to contact this man, I contacted him and he guided me on how to purchase for the medicine. I asked him for solutions and he started the remedies for my health. Thank God, now everything is fine, I’m cured by Dr. UCHEGBU herbal medicine, I’m very grateful to Dr. UCHEGBU, reach him now on ([email protected] ) or you can also call him on 2347034798638.

Dr. UCHEGBU Also Cures:


2. HERPES 1/2


4. ALS (Lou Gehrig’s disease)

5. Hepatitis B

6. chronic pancreatic

7. Emphysema

8. COPD (Chronic Obstructive Pulmonary Disease)

9. Asthma

10.Acute angle-closure Glaucoma

11. Diabetes



Anita Ford
April 06, 2020
I am so Happy to be writing this article in here, i am here to explore blogs forum about the wonderful and most safe cure for HERPES SIMPLEX VIRUS . I was positive to the deadly Virus called HERPES and i lost hope completely because i was rejected even by my closet friends. i searched online to know and inquire about cure for HERPES and i saw Dr uchegbu testimony online on how he was cured so many persons from Herpes Disease so i decided to contact the great herbalist because i know that nature has the power to heal everything. i contacted him to know how he can help me and he told me never to worry that he will help me with the natural herbs from God! after 2 days of contacting him, he told me that the cure has been ready and he sent it to me via FEDEX or DHL or UPS and it got to me after 4 days! i used the medicine as he instructed me (MORNING and EVENING) and i was cured! its really like a dream but i'm so happy! that's the reason i decided to also add more comment of Him so that more people can be saved just like me! and if you need his help,contact his Email: ([email protected]) you can contact him on mobile number 2347034798638

He have the herb to cure difference cure for any sickness









(9) ASTHMA...
wanda davis
April 04, 2020
Must read! I'm from US taxes, for a year now i have been living with this virus called HERPES VIRUS and i have been taking some medications from my Doctor and there was no improvement, All thanks to God almighty for using Dr Aza for curing my Herpes Virus with the help of his powerful root and herbs...Well i do not have much to say, with all my life i will for ever be grateful to him and God Almighty for using Dr Aza to reach me when i thought it is all over, today i am now happy after the medical doctor have confirmed my status Negative, i have never in my life believed that HERPES could be cure by any herbal medicine. so i want to use this medium to reach other persons who is suffering from any deadly disease or herpesvirus you can contact Dr Aza on his email, [email protected]  or call/whatsapp  1(315)7951518 Thanks.

Mercy Kelvin
April 04, 2020
Herpes Cure

Indeed doctor Ahmed has a cure for Herpes Virus

I was once victim of the herpes virus with many epidemics on my body, I was cured of the virus thanks to the help of doctor Ahmed Usman herbal medicine. I have met most of his patient testimonials on blogs and social media pages, cured of various illnesses. I contacted him with his email address to which he replied and asked me a few questions and the preparation method for which I paid, he sent me herbal medicines and with his prescription I drank herbal medicine for 21 days and the epidemics on my body were healed after concluding herbal medicine, I went for the test and my result was negative with no trace of virus on my blood. You can also be cured, contact him on his official email; [email protected] or via whatsapp 2348064460510

He said he had an herbal remedy for

diabetes, cancer, fibroid, hyperglycemia, hepatitis,

HIV, heart disease and liver disease.
juwan james
April 01, 2020
Dr Ishiaku herbal medicine is mighty and genuine,I use to use Mellisa oil and Lavender Healing herbs but result were just still the same.But using Doctor Ishiaku herbal medicine cured my herpes final and I have being living for 3 years now No Sores.My herpes is truely gone.Contact him if you interested of Whatsapp Number On 2348180828544...
Amalia Dorothea
April 01, 2020
I was diagnosed of herpes virus, I have tried all possible means to get cure but all my effort proved abortive, until a friend of mine introduced me to a herbal doctor called Chief Dr Ejiehiwase, who prepare herbal medicine to cure all kind of diseases including herpes virus (Herpes), when i contacted this herbal doctor via his email, he sent me herpes virus herbal medicine via courier service, when i received the herbal medicine he gave me step by step instructions on how to apply it, when i applied it as instructed i was totally cured from the virus within 3 weeks of usage. Contact this great herbal doctor today to get your cure.

Via Email : [email protected]

Whats App : 2348110850281

May 21, 2020
Hello Everyone out there,I am here to give my testimony about a Herbalist doctor who helped me . I was infected with HERPES VIRUS in 2012, i went to many hospitals for cure but there was no solution, so I was thinking how can I get a solution out so that my body can be okay. One day I was in the river side thinking where I can go to get solution. so a lady walked to me telling me why am I so sad and i open up all to her telling her my problem, she told me that she can help me out, she introduce me to a doctor who uses herbal medication to cure HERPES VIRUS and gave me his email, so i mail him. He told me all the things I need to do and also give me instructions to take, which I followed properly. Before I knew what is happening after two weeks the HERPES VIRUS that was in my body got vanished . so if you are also heart broken and also need a help, you can also email him at Email [email protected] or Whats-app : 2349037520482 .Contact him today and you will have a testimony…Good luck!... DOCTOR OZ CAN AS WELL CURE THE FOLLOWING DISEASE:-1. HIV/AIDS. HERPES. CANCER. ALS. Hepatitis Diabetes LOVE SPELL IF YOU NEED YOUR EX LOVER BACK TO LOVE YOU AGAIN.
Comments are back! Simply post the comment (it'll complain about you failing the human test) then simply click on the captcha and then click "Post Comment" again. Comments are also welcome on our Facebook page.