Therapeutic target for alcohol abuse
US researchers raise hopes of new treatment for alcoholism.
Many of us head straight to the pub after a tough week at work but stress-induced drinking can become a serious problem for some. Although psychosocial therapy has a good success rate in encouraging abstinence among alcoholics, the relapse rate is high, with 40 to 70 per cent returning to drink within the first year of giving up alcohol, with stress being a prominent factor. Now a team of US researchers claims to have found a link between a key brain receptor and alcohol abuse, which could lead to future treatments to help prevent people from hitting the bottle.
A research team from the Scripps Research Institute in La Jolla, California, and Duke University, Durham, focused on the central amygdala (CeA), a region of the brain which is involved in alcohol reward and dependence. This part of the brain has an abundance of a chemical called corticotropin-releasing factor (CRF), which is frequently implicated in stress-related disorders such as anxiety and depression. The researchers wanted to test a theory that ethanol mimics CRF by acting on presynaptic CRF receptors to increase the release of GABA (?-aminobutyric acid), which is known to have a calming effect on neurological activity.
They performed electro-physiological recordings of neurones in slices of CeA from both wild-type mice and from mice that had been genetically engineered to have no CRF receptor. In wild-type mice, both CRF and ethanol enhanced GABA-mediated neurotransmission in CeA neurones. However, in mice lacking the CRF receptor, or after treatment with CRF antagonists, neither ethanol nor CRF altered the GABA activity.
Chris Bailey, from the University of Bristol's pharmacology department, described the team's findings as 'exciting'. However, he said that 'it seems initially surprising that CRF and ethanol share a common mechanism, since CRF is thought to enhance stress-related behaviour, whereas ethanol reduces it'.
The team suggests that its work backs the theory that CRF receptors could 'represent an important therapeutic target for the treatment of stress-induced alcohol drinking'. George Siggins, who headed the research team, told Chemistry World that he expects clinical trials with one or more CRF1 receptor agonists within the year. According to Bailey, 'several targets have already been identified for controlling relapse in recovering alcoholics, but these have had limited clinical efficacy, often because they are complicated by low compliance by patients. Time will tell whether a drug which might be expected to reduce stress-related behaviour results in increased compliance, and therefore an increased success rate'.
Z Nie et al, Science, 2004, 303, 1512