Navigation Links
A new target for alcoholism treatment: Kappa opioid receptors

Philadelphia, PA, May 22, 2014 The list of brain receptor targets for opiates reads like a fraternity: Mu Delta Kappa. The mu opioid receptor is the primary target for morphine and endogenous opioids like endorphin, whereas the delta opioid receptor shows the highest affinity for endogenous enkephalins. The kappa opioid receptor (KOR) is very interesting, but the least understood of the opiate receptor family.

Until now, the mu opioid receptor received the most attention in alcoholism research. Naltrexone, a drug approved by the U.S. Food and Drug Administration for the treatment of alcoholism, acts by blocking opiate action at brain receptors and is most potent at the mu opioid receptor. In addition, research has suggested that a variant of the gene that codes for the mu opioid receptor (OPRM1) may be associated with the risk for alcoholism and the response to naltrexone treatment.

However, naltrexone also acts at the kappa opioid receptor and it has not been clear whether this effect of naltrexone is relevant to alcoholism treatment.

A growing body of research in animals implicates the KOR in alcoholism. Stimulation of the KOR, which occurs with alcohol intake, is thought to produce unpleasant and aversive effects. This receptor is hypothesized to play a role in alcohol dependence, at least in part, by promoting negative reinforcement processes. In other words, the theory postulates that during development of alcohol dependence, the KOR system becomes overstimulated, producing dysphoria and anhedonia, which then leads to further alcohol seeking and escalation of alcohol intake that serves to self-medicate those negative symptoms.

A new study in Biological Psychiatry, led by Dr. Brendan Walker at Washington State University, used a rat model of alcohol dependence to directly investigate the KOR system following chronic alcohol exposure and withdrawal.

They found that the KOR system is dysregulated in the amygdala of alcohol-dependent rats, a vital brain region with many functions, including regulation of emotional behavior and decision-making. Chronic alcohol consumption is known to cause neuroadaptations in the amygdala. In this study specifically, they found increased dynorphin A and increased KOR signaling in the amygdala of alcohol-dependent rats.

When the rats were in acute alcohol withdrawal, the researchers administered different drugs, each of which target the KOR system in precise ways, directly into the amygdala. Using this site-specific antagonism, they observed that alcohol dependence-related KOR dysregulation directly contributes to the excessive alcohol consumption that occurs during withdrawal.

"These data provide important new support for the hypothesis that kappa opioid receptor blockers might play a role in the treatment of alcoholism," said Dr. John Krystal, Editor of Biological Psychiatry. "This study suggests that one role might be to prevent a relapse to alcohol use among patients recently withdrawn from alcohol."

"This dataset demonstrates the extensive nature of the neuroadaptations the brain undergoes when chronically exposed to alcohol. The implications of these results are far reaching and should help guide pharmacotherapeutic development efforts for the treatment of alcohol use disorders," said Walker. "Pharmacological compounds that alleviate the negative emotional / mood states that accompany alcohol withdrawal, by attenuating the excessive signaling in the dynorphin / kappa-opioid receptor system, should result in enhanced treatment compliance and facilitate the transition away from alcohol dependence."

Additional extensive research will be necessary to identify and test the effectiveness of specific drugs that act on the KOR system, but these findings provide researchers with a potentially successful path forward to developing new drugs for the treatment of alcoholism.


Contact: Rhiannon Bugno

Related medicine news :

1. Drug-target database lets researchers match old drugs to new uses
2. Genomic tumor testing to match lung cancer patients with targeted drugs transforms care
3. RELAX-AHF and PROTECT studies find targeting WHF may reduce readmissions and save lives
4. New treatment targeting versatile protein may protect brain cells in Parkinsons disease
5. Novel target found for chemotherapy-resistant leukemia cells
6. Scientists find way to target cells resistant to chemo
7. Gold nanoparticles help target, quantify breast cancer segments in a living cell
8. Non-uniform genetic mutations identified in lung cancers could lead to targeted treatment
9. FDA approves first targeted drug for advanced stomach cancer
10. New pain relief targets discovered
11. CU researchers discover target for treating dengue fever
Post Your Comments:
(Date:11/25/2015)... (PRWEB) , ... November 25, 2015 , ... ... ) has focused on providing comprehensive solutions involving adult stem cell therapies to ... has officially deemed the “Regenestem” name as a Registered Trademark (RTM). , Organizations ...
(Date:11/24/2015)... ... November 25, 2015 , ... Genesis Chiropractic Software helps practice ... an agreement between the practice owner and the patient that automatically manages all ... projections. Click here to learn more. , According to ...
(Date:11/24/2015)... ... 2015 , ... New patients who wish to seek treatment for missing teeth ... at her Mississauga, ON practice. Dr. Williams has been providing dental service for over ... , Missing teeth can lead to a variety of complications if they are not ...
(Date:11/24/2015)... , ... November 24, 2015 , ... ... launched their Black Friday sale a week early, offering 40% off select bras ... the intimate apparel industry through both mobile fit technology and the latest fashion, ...
(Date:11/24/2015)... ... November 24, 2015 , ... DMG Productions announced that they will feature ... quarter 2016 via Discovery Channel. Dates and show times TBA. , Aphria, Inc., is ... the business of producing and supplying medical marijuana pursuant to the Marijuana for Medical ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... -- The hope of bearing a child ... cycles. After failure of over 15 IVF cycles, Mrs. ... hopes that she would be able to conceive ever. But finally optimism prevailed as she ... of over 15 IVF cycles. India ... one last attempt with Gaudium IVF Center in New ...
(Date:11/24/2015)...  Thanks to a donor with a personal connection ... Sister Diane Grassilli Center for Women,s Health now offers ... San Francisco . Fred Ruhland ... a gift of $617,320 that allowed the Center to ... and Whole Breast Ultrasound. Tomosynthesis, three-dimensional (3-D) mammography for ...
(Date:11/24/2015)... Colo. , Nov. 24, 2015  Array ... that its Chief Executive Officer, Ron Squarer ... Healthcare Conference in New York.  The public is ... webcast on the Array BioPharma website.Event:Piper Jaffray Annual ... , Wednesday, December 2, 2015Time:1:30 p.m. Eastern Time ...
Breaking Medicine Technology: