Scientists have underlined the potential of an endogenous anti-stress peptide in the brain can help prevent and even reverse some of the cellular effects of acute alcohol and alcohol dependence in animal models.
The work by scientists at the Scripps Research Institute could lead to the development of novel drugs to treat alcoholism.
AdvertisementSpecifically, the study led by Scripps Research Associate Professor Marisa Roberto examined the interaction between two competing agents-one a stress peptide that promotes excessive alcohol drinking, the other an anti-stress peptide that opposes it.
The results confirm that drugs derived from the anti-stress peptide nociceptin could play an important role in treating a complex and multi-faceted disease.
Roberto and her team focus on the central nucleus of the amygdala, a region of the brain that has long been implicated in the elevated anxiety and excessive drinking associated with alcohol dependence and withdrawal.
In previous animal studies, Roberto and her colleagues demonstrated that a particular stress peptide produced in the amygdala, corticotropin-releasing factor (CRF), plays a key role in the transition from alcohol use to alcohol dependence.
They also demonstrated that nociceptin, a peptide that structurally resembles endogenous opioids, can both prevent and reverse some effects of alcohol.
At the behavioural level, nociceptin regulates anxiety and alcohol drinking in rats.
To find out if nociceptin blocked the effect of CRF on a cellular level, the scientists examined amygdala neurons from both alcohol-dependent and control rats.
They added CRF and nociceptin and electrically stimulated the neurons to see how they would behave under the influence of both peptides. The result: nociceptin completely blocked the effects of CRF on GABA release.
"No matter when CRF is added, nociceptin wins. That's a really consistent effect," said Roberto.
The study has been published online by the journal Biological Psychiatry.