New research has implicated the Kappa Opioid Receptor (KOR)—the primary target for morphine and endogenous opioids— in alcoholism. The delta opioid receptor on the other hand shows high affinity for endogenous enkephalins. KOR is the least understood of the opiate receptor family.
Until now alcoholism research focussed primarily on the mu opioid receptor. The FDA approved drug for alcoholics called Naltrexone, for example, acts essentially by blocking opiate action at the mu opioid receptor. The fact, however, is that naltrexone also acts at the kappa opioid receptor. Up until now it has not been clear whether this effect of naltrexone is relevant to alcoholism treatment.
It is being believed that the stimulation of the KOR, which occurs with alcohol intake, produces unpleasant and aversive effects. The hypothesis is that alcohol dependence, at least in part, is caused by promoting negative reinforcement processes.
In other words, even as alcohol dependence develops the KOR system gets excessively stimulated, producing dysphoria and anhedonia. These aggravate the craving for alcohol, which in turn leads to its higher intake.
The KOR system in the amygdala of alcohol-dependent rats is dysregulated according to a new study in Biological Psychiatry, led by Dr Brendan Walker at Washington State University. The amygdala is a vital brain region which controls many functions including emotional behaviour and decision-making.
Neuroadaptations in the amygdala are attributed to chronic alcohol consumption. In this study increased dynorphin A and KOR signalling were found in the amygdala of alcohol-dependent rats.
The study, which involved the administration of different drugs targeting the KOR system directly into the amygdala, proved that alcohol dependence-related KOR dysregulation contributes directly to excessive alcohol consumption.
“The data supports the hypothesis that kappa opioid receptor blockers might have a role to play in treating 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 “This study suggests that one role might be to prevent a relapse to alcohol use among patients recently withdrawn from alcohol.”
These findings have far reaching implications for the treatment of alcohol use disorders, said Walker. “Pharmacological compounds that alleviate the mood states, which accompany alcohol withdrawal, should result in enhanced treatment compliance and facilitate the transition away from alcohol dependence.”