Dopaminergic neurotoxin administration to the area of the suprachiasmatic nuclei induces insulin resistance.

DOPAMINERGIC neuron neurotoxin (6-hydroxy-dopamine ; 6-OHDA) administration directed to the hypothalamic area of the mammalian pacemaker, the suprachiasmatic nuclei (SCN), was carried out on lean, glucose tolerant hamsters to investigate the possibility that dopaminergic input to the vicinity of the SCN is necessary to maintain this metabolic condition. Glucose tolerance tests (GTT, 3 g glucose/kg) were performed 4 days prior to and 16 days after neurotoxin lesioning. 6-OHDA administration to the area of the SCN resulted in both a significant 58% increase in daily food consumption by the 16th day post-lesioning, and a 85% increase in weight gain 4 and 8 weeks after lesioning relative to controls. Such treatment also significantly increased the total areas under the GTT glucose and insulin curves by 48% and 400% respectively, compared with controls. These findings indicate that body weight gain, glucose intolerance and insulin resistance result from decreased dopaminergic input to the area of the SCN.