HYPOTHALAMIC MONOAMINES AND INSULIN IN RELATION TO FEEDING IN THE GENETICALLY-OBESE ZUCKER RAT AS REVEALED BY MICRODIALYSIS

Dynamic changes in VMH and PVN monoamines and immunoreactive insulin ( IRT) were investigated by microdialysis in freely-moving genetically o bese Zucker rats in order to relate possible disturbances to the impai red regulation of food intake of this model. Serotonin (5-HT), 5-HIAA and dopamine (DA) increased at the beginning of spontaneous meals whil e DOPAC decreased. Although similar in normal and obese rats, these ch anges were much more dramatic in the latter, as if more ''signal'' for satiety were necessary at the VMH-PVN level. Glucoprivic feeding or s atiety 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 i ncreases in 5-HIAA and DOPAC), but the occurrence of meals, in the obe se, showed a superimposition of monoaminergic changes resembling those related to spontaneous feeding. The monoaminergic effects of insulin must therefore be dissociated from its effects on feeding. Hypothalami c 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 sche duled meals, a similar anticipatory increase in IRI was found in both obese and lean rats. This suggests that brain insulin is more than a s atiety signal. In addition, in response to an i.v. insulin infusion, I RI increased twice as much in obese rats despite lower basal levels. W hatever the origin of hypothalamic insulin, the larger response of the obese Zucker rat, known to be insulin resistant, may reflect the inef ficiency of the peptide in reducing feeding and body weight in this pa thological model.