In these studies we will examine the relationship of the neurochemical abnormalities found in two strains of genetically obese-diabetic mutant mice with the syndromes demonstrated by these mutations. We have found that both the obob and dbdb mutations have significantly elevated levels of hypothalamic norepinephrine. We have studied this finding in more detail in the obob mutant and have found that there are also significantly increased numbers of alpha-receptors in the hypothalamus of the obob mouse. Although the receptor density is increased, there is no change in affinity. In the future we intend to conduct similar studies in the dbdb mutant and to extend our analysis to include the alpha-2 receptor and the beta receptor. We will also conduct studies to more specifically identify the regions of the hypothalamus where the excess norepinephrine is located. This will be done by removing individual nuclei and determining their norepinephrine and dopamine content. Other studies will examine the effects of specific pharmacological agents on both the neurochemistry and food intake of the mutant mice.