There are potential implications of GABAB1 splicing changes in alcoholic prefrontal cortices. First, optimal function of this brain region is required for decision making and reward pathway regulation, and prefrontal cortex function reduction is linked with dependence on alcohol and other drugs (5, 41, 42). Second, genetic and genomic analyses of excessive alcohol consumption in rodent models and humans point to a critical role of GABAergic transmission (38, 43). Third, drugs acting on GABAB receptors have been used for alcoholism treatment. In particular, baclofen, a GABAB agonist, may be effective at high doses (4) but was not beneficial at lower doses (44).Thus, it is possible that the GABAB receptor remodeling by chronic alcohol abuse may be one reason that reduce its effectiveness, requiring higher than expected doses of baclofen needed for successful treatment.
