Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activation

The toxin-antibody complex anti-d betah-saporin (DSAP) selectively destroys d betah-containing catecholamine neurons. To test the role of specific cat echolamine neurons in glucoregulatory feeding and adrenal medullary secreti on, we injected DSAP, unconjugated saporin (SAP), or saline bilaterally int o the paraventricular nucleus of the hypothalamus (PVH) or spinal cord (T2- T4) and subsequently tested rats for 2-deoxy-D-glucose (2DG)-induced feedin g and blood glucose responses. Injections of DSAP into the PVH abolished 2D G-induced feeding, but not hyperglycemia. 2DG-induced Fos expression was pr ofoundly reduced or abolished in the PVH, but not in the adrenal medulla. T he PVH DSAP injections caused a nearly complete loss of tyrosine hydroxylas e immunoreactive (TH-ir) neurons in the area of A1/C1 overlap and severe re duction of A2, C2, C3 (primarily the periventricular portion), and A6 cell groups. Spinal cord DSAP blocked 2DG-induced hyperglycemia but not feeding. 2DG-induced Fos-ir was abolished in the adrenal medulla but not in the PVH . Spinal cord DSAP caused a nearly complete loss of TH-ir in cell groups A5 , A7, subcoeruleus, and retrofacial C1 and a partial destruction of C3 (pri marily the ventral portion) and A6. Saline and SAP control injections did n ot cause deficits in 2DG-induced feeding, hyperglycemia, or Fos expression and did not damage catecholamine neurons. DSAP eliminated d betah immunorea ctivity but did not cause significant nonspecific damage at injection sites . The results demonstrate that hindbrain catecholamine neurons are essentia l components of the circuitry for glucoprivic control of feeding and adrena l medullary secretion and indicate that these responses are mediated by dif ferent subpopulations of catecholamine neurons. J. Comp. Neurol. 432:197-21 6, 2001. (C) 2001 Wiley-Liss, Inc.