Effects of chronic administration of sibutramine on body weight, food intake and motor activity in neonatally monosodium glutamate-treated obese female rats: Relationship of antiobesity effect with monoamines

When the hypothalamic ventromedial nucleus and arcuate nucleus were destroy ed in rats by treatment with monosodium glutamate in the neonatal stage, in crease in the Lee index (body weight (1/3)/body length) and in retroperiton eal fat as well as decreases in spontaneous motor activity, food consumptio n and growth hormone secretion function associated with hypothalamic low bo dy length obesity (monosodium glutamate-treated obesity; MSG-OB) were obser ved as these rats grew. Treatment with sibutramine at 3 and 10 mg/kg p.o. o nce a day continuously for 14 days improved these parameters, and the degre e of improvement was dose related. The plasma lipid values in MSG-OB rats, which were the same as those in normal rats, were decreased by consecutive administration of sibutramine. Levels of hypothalamic monoamines (MAs) such as norepinephrine, 5-HT (serotonin) and dopamine and their metabolites DOP AC, HVA and 5-HIAA were decreased in MSG-OB rats, and further decrease in t hem, though slight, was observed with consecutive daily administration of s ibutramine, probably as a result of the feedback attributable to an increas e in MA in synapses caused by inhibition of MA uptake by sibutramine. These results suggest that sibutramine can activate the MA nervous system by MA uptake inhibition in regions of the brain such as the lateral hypothalamic area and the paraventricular nucleus, which control food intake and sympath etic nerve activity, and the nigrostriatal area related to the extrapyramid al motor system, and thereby exhibit anti-obesity effects in the MSG-OB rat .