Hypothalamic monoamines and insulin in relation to feeding in the genetically obese Zucker rat as revealed by...

Dynamic changes in VMH and PVN monoamines and immunoreactive insulin (IRI) were investigated by microdialysis in freely-moving genetically obese Zucker rats in order to relate possible disturbances to the impaired regulation of food intake of this model. Serotonin (5-HT), 5-HIAA and dopamine (DA) increased at the beginning of spontaneous meals while DOPAC decreased. Although similar in normal and obese rats, these changes were much more dramatic in the latter, as if more "signal" for satiety were necessary at the VMH-PVN level. Glucoprivic feeding or satiety are induced in normal rats by intravenous infusions of insulin or insulin+glucose respectively. The Zucker rat is resistant to these treatments. The monoaminergic changes brought about by these infusions were similar in obese and normal rats (decreases in 5-HT and DA and increases in 5-HIAA and DOPAC), but the occurrence of meals, in the obese, showed a superim-position of monoaminergic changes resembling those related to spontaneous feeding. The monoaminergic effects of insulin must therefore be dissociated from its effects on feeding. Hypothalamic insulin itself might be the brain signal. At the beginning of meals presented for the first time, VMH-PVN IRI increased earlier and with a smaller magnitude in the obese. When the rats were accustomed to scheduled meals, a similar anticipatory increase in IRI was found in both obese and lean rats. This suggests that brain insulin is more than a satiety signal. In addition, in response to an i.v. insulin infusion, IRI increased twice as much in obese rats despite lower basal levels. Whatever the origin of hypothalamic insulin, the larger response of the obese Zucker rat, known to be insulin resistant, may reflect the inefficiency of the peptide in reducing feeding and body weight in this pathological model.