Association of altered brain norephinephrine and serotonin with the obesity induced by goldthioglucose in mice.

Two experiments examined the possibility that mice rendered obese by systemic injection of goldthioglucose (GTG) possess altered endogenous levels of brain norepinephrine (NE), dopamine (DA), serotonin (5-hydroxytryptamine or 5HT) and/or 5-hydroxyindoleacetic acid (5HIAA). In the first experiment, single-housed GTG-obese mice were found to have normal brain DA and 5HIAA but 14% less NE and 6% less 5HT than controls. This neurochemical profile was strikingly similar to that previously reported for rats rendered obese by ventromedial hypothalamic lesions (i.e., normal DA and 5HIAA, 19% less NE, 7% less 5HT). However, in the second experiment, equally obese GTG mice pair-housed with non-obese controls showed normal DA, 5HIAA, and NE but 9% more 5HT than controls. In other words, absolute levels of these brain substances were inconsistent with respect to obesity across experiments. On the other hand, when ratios of all possible combinations of these compounds were compared across experiments, only 5HT/NE ratios were consistently different (higher) in GTG mice. In addition, reliable inverse correlations were obtained between weight gain parameters and brain 5HT/NE or 5HIAA/NE ratios for GTG mice. These findings suggest that interactions between brain 5HT and NE neurons may contribute to the overeating and obesity which occur in mice after GTG administration.