BROMOCRIPTINE REDUCES OBESITY, GLUCOSE-INTOLERANCE AND EXTRACELLULAR MONOAMINE METABOLITE LEVELS IN THE VENTROMEDIAL HYPOTHALAMUS OF SYRIAN-HAMSTERS

We examined whether reductions in body fat stores and insulin resistan ce in Syrian hamsters induced by bromocriptine are associated with red uctions in daily norepinephrine (NE) and serotonin activities as indic ated by their extracellular metabolite levels in the ventromedial hypo thalamus (VMH). High levels of these monoamines within the VMH have be en suspected to induce obesity and insulin resistance. Microdialysate samples from the VMH of freely moving obese male hamsters (BW: 208 +/- 5 g) were collected hourly over a 25-hour period before bromocriptine treatment, during the first day of and after 2 weeks of bromocriptine treatment (800 mu g/animal daily, i.p.), and body composition and glu cose tolerance analyses were conducted before and after 2 weeks of tre atments. The microdialysate samples were analyzed by HPLC for metaboli tes of serotonin: 5-hydroxy-indoleacetic acid (5-HIAA), NE: 3-methoxy- 4-hydroxy-phenylglycol (MHPG), and dopamine: homovanillic acid (HVA). Bromocriptine treatment for 14 days significantly reduced body fat by 60% and areas under the glucose and insulin curves during a glucose to lerance test by 50 and 46%, respectively. Concurrently, extracellular VMH contents of 5-HIAA, MHPG, and HVA were reduced by 50, 29 and 66%, respectively (p < 0.05). Similarly, VMH 5-HIAA and MHPG contents were 48 and 44% less, respectively (p < 0.05), in naturally glucose-toleran t hamsters compared with naturally glucose-intolerant hamsters. Bromoc riptine induced reductions of body fat, and improvements in glucose in tolerance may result in part from its ability to decrease serotonin an d NE activities in the VMH.