Hypothalamic catecholamine systems in genetically obese mice (obob): Decreased sensitivity to reserpine treatment

Significantly elevated levels of hypothalamic norepinephrine (NE) and pituitary dopamine (DA) have been reported in genetically obese mice ( obob). In the current study, significant differences were found between obese and lean mice in their response to reserpine treatment. Although reserpine produced significant decreases in hypothalamic NE content in obese mice, the NE levels in obese mice decreased more slowly over time than those in lean mice, and were always significantly higher in obese mice than in lean mice. Hypothalamic DA depletions also occurred more slowly in obese than in lean mice, but the final degree of the depletion did not differ between the two groups. The DA content of the pituitary and the NE content of several peripheral tissues (heart, kidney, spleen) were depleted equally in obese and lean mice by the reserpine treatment. The incomplete and/or delayed depletion of the hypothalamic catecholamines in the obese mice did not appear to result from the distribution of less reserpine to the hypothalamus of the obese mice, and could not be overcome by administering a high dose of reserpine to obese mice. The residual NE found in the hypothalamus of obese mice after reserpine treatment apparently was not newly synthesized because inhibition of NE synthesis in these animals failed to reduce significantly the amount of the NE excess remaining. The results indicate that although a substantial portion of the hypothalamic NE excess found in obese mice is reserpine-sensitive, the hypothalamic catecholamine systems of obese mice, when compared to those of similarly treated lean mice, respond abnormally to reserpine treatment.