Decreased alcohol consumption and anxiolysis in the area postrema lesion rat model of food motivated behavior

Current research into the neurochemicals and pathways that underlie diseases such as alcoholism and anxiety indicates a role for neuropeptide Y (NPY) in the etiology of these disorders. Indeed, rodent models that either over express or do not express NPY in the brain display overt symptoms of both of these disorders. Data that has been generated elsewhere strongly suggests an inverse correlation between NPY and alcoholism or anxiety. Since both of these diseases exert a heavy toll in costs on the American health care system, further research into the involvement of NPY in the etiology of alcoholism or anxiety would potentially benefit therapies directed toward these disorders. Our laboratory studies a rodent model of motivated food behavior which is the area postrema (APX) lesioned rat. APX rats have long been known to overconsume palatable foods such as cookies or sweetened condensed milk. Although it is probable that this behavior in the APX rat is due to aberrations involving neural reward circuits, APX rats have also been shown to express high levels of NPY mRNA and protein in the hypothalamus. It is thought that this increase in hypothalamic NPY might contribute to the overconsumption of palatable foods in this model. Since APX rats voraciously overconsume palatable foods as well as salt solutions, we examined their consumption of alcohol and found that instead of overconsuming alcohol, they avoided it when compared to a sham-lesioned control rat. Considering the established role for NPY in anxiety in rodents, we next examined APX rats in the open field test and elevated plus maze; both are measures of anxiety. In both tests, the area postrema lesion increased anxiolytic behavior. We then examined NPY mRNA and protein levels in APX rats and found increased levels in limbic regions. The increase in NPY in APX rats may account for anxiolytic behavior and alcohol aversion in this model and provides further evidence supporting a role for NPY in both of these disorders.