SEROTONERGIC ACTIVITY IS DEPRESSED IN THE VENTROMEDIAL HYPOTHALAMIC NUCLEUS OF 12-DAY-OLD OBESE ZUCKER RATS

We previously reported lower ventromedial hypothalamic nucleus (VMN) s erotonergic activity in ll-wk genetically obese vs. lean Zucker rats. To determine whether the activity was secondary to metabolic alteratio ns associated with this established obesity (e.g., significant hyperph agia and hyperinsulinemia), we examined monoaminergic activity in vari ous brain nuclei of 12-day lean (Fa/Fa and Fa/fa) and obese (falfa) ra ts early in the development of obesity. Obese pups had greater percent carcass fat than heterozygotes, both of which were fatter than homozy gous lean rats. Obese, but not heterozygous lean, pups were hyperinsul inemic vs. Fa/Fa pups. VMN 5-hydroxy-3-indoleacetic acid levels, an in dex of serotonin release, were lower in obese and heterozygous than in homozygous lean pups and were not correlated with plasma insulin leve ls. Although monoamine differences also occurred in several other nucl ei, for the most part they appeared to be unrelated to the obese genot ype. We conclude that blunted VMN serotonergic activity is not seconda ry to the obese rat's hyperinsulinemia and may play a significant role in the development of obesity.