Navigation Links
A new target for alcoholism treatment: Kappa opioid receptors
Date:5/22/2014

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
Biol.Psych@utsouthwestern.edu
214-648-0880
Elsevier
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:7/23/2017)... , ... July 23, 2017 , ... ... thus improving communication, safety and patient-provider relationships. New tools are helping patients become ... of the 19th Annual Health Care’s Most Wired® survey, released today by the ...
(Date:7/22/2017)... ... July 21, 2017 , ... Reassured For Life ( http://www.reassured.ca ), is now ... owner and licensed broker Nerissa McNaughton. “I launched this firm because I know talking ... a very necessary conversation. I make it easy. As a broker I have access ...
(Date:7/21/2017)... CO (PRWEB) , ... July 21, 2017 , ... ... insurance management assistance and financial consultations to communities in the greater Denver region, ... Denver native recently diagnosed with a very rare kind of epilepsy. , Until ...
(Date:7/21/2017)... ... 2017 , ... Fresh Wave® IAQ today announced the launch of its innovative ... universities at the APPA 2017 Annual Conference and Exhibition in Booth #414. ... without the use of harsh chemicals, Fresh Wave IAQ Smoke Away Air & Fabric ...
(Date:7/21/2017)... ... ... The House of Yahweh in Abilene, Texas, has written a new post this week that ... to be more open about positive changes. Yisrayl says the use of force is not ... positive way to solve all; yes, all issues, and he is ready to share this ...
Breaking Medicine News(10 mins):
(Date:7/11/2017)... 11, 2017 Oramed Pharmaceuticals Inc. (NASDAQ: ... company focused on the development of oral drug delivery ... Administration (FDA) has agreed to schedule an End-of-Phase II ... trial of its oral insulin capsule ORMD-0801 in the ... met primary and secondary endpoints by indicating a statistically ...
(Date:7/10/2017)... , July 10, 2017 The Institute ... test methods, is the recipient of a VITROCELL® inhalation ... PETA International Science Consortium. The device, which is designed ... to expose human lung cells to airborne test materials ... will use the VITROCELL® system for testing combustible tobacco ...
(Date:7/10/2017)... 2017  The tenth annual BioPharm America™ ... at the Sheraton Boston Hotel, September 26–27. The ... global decision makers and innovative biotech startup companies. The ... during two impactful days. BioPharm America is now part ... networking opportunities with 4,500+ life science industry influencers participating ...
Breaking Medicine Technology: