Dorsomedial hindbrain participation in glucoprivic feeding response to 2DG but not 2DG-induced hyperglycemia or activation of the HPA axis.

2-Deoxy-d-glucose (2DG) is a glucose analogue that inhibits intracellular utilization of glucose and produces a characteristic behavioral response known as glucoprivic feeding. The area postrema (AP) is a caudal hindbrain structure shown previously to be involved in 2DG-induced glucoprivic feeding. In addition, peripheral administration of 2DG is known to elicit activation of both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenomedullary system. The neural substrates for these neuroendocrine and neural responses to 2DG are not known although they may also involve the AP. The possible role of the AP in 2DG-induced feeding, activation of the HPA axis and hyperglycemia was investigated in Sprague-Dawley rats with lesions centered on the area postrema (APX) and sham-operated (SHM) rats administered 2DG (200 mg/kg) or physiological saline (1 ml/kg). Peripheral administration of 2DG evoked a feeding response in SHM rats that was abolished in APX animals. Interestingly, 2DG administered at this dose produced a significant increase in plasma corticosterone and plasma glucose in both SHM and APX rats for up to 4 h after drug treatment. Collectively, these findings suggest that the AP is involved in the behavioral (feeding) response to peripheral administration of 2DG, but does not appear to be a common neural substrate for the neuroendocrine (HPA axis) and sympathoadrenal (hyperglycemic) responses to this agent.