The toxin-antibody complex anti-d(beta)h-saporin (DSAP) selectively destroys d(beta)h-containing catecholamine neurons. To test the role of specific catecholamine neurons in glucoregulatory feeding and adrenal medullary secretion, we injected DSAP, unconjugated saporin (SAP), or saline bilaterally into the paraventricular nucleus of the hypothalamus (PVH) or spinal cord (T2-T4) and subsequently tested rats for 2-deoxy-D-glucose (2DG)-induced feeding and blood glucose responses. Injections of DSAP into the PVH abolished 2DG-induced feeding, but not hyperglycemia. 2DG-induced Fos expression was profoundly reduced or abolished in the PVH, but not in the adrenal medulla. The PVH DSAP injections caused a nearly complete loss of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the area of A1/C1 overlap and severe reduction 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 (primarily the ventral portion) and A6. Saline and SAP control injections did not cause deficits in 2DG-induced feeding, hyperglycemia, or Fos expression and did not damage catecholamine neurons. DSAP eliminated d(beta)h immunoreactivity but did not cause significant nonspecific damage at injection sites. The results demonstrate that hindbrain catecholamine neurons are essential components of the circuitry for glucoprivic control of feeding and adrenal medullary secretion and indicate that these responses are mediated by different subpopulations of catecholamine neurons.

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Hindbrain norepinephrine (NE) and epinephrine (E) neurons play a pivotal role in the central distribution of sensory signals derived from the internal environment. Their projections influence the various secretory patterns of the hypothalamo-pituitary-adrenal axis and are essential for feeding and adrenal medullary responses to glucoprivation. NE and E terminals in the paraventricular nucleus of the hypothalamus (PVH) and associated hindbrain cell bodies can be virtually eliminated by PVH microinjection of a retrogradely transported conjugate of saporin (SAP, a ribosomal toxin) and a monoclonal antibody against dopamine beta-hydroxylase (dbetah), i.e. dbetah mouse monoclonal antibody conjugated to SAP (DSAP). To examine the effects of selective elimination of NE/E afferents on hypothalamo-pituitary-adrenal activation, we injected DSAP into the PVH and measured corticosterone secretion under basal circadian conditions and in response to two distinct challenges: glucoprivation and forced swim. DSAP lesions profoundly impaired glucoprivation-induced corticosterone secretion and induction of CRH heteronuclear RNA and Fos mRNA in the PVH, without impairing basal CRH mRNA expression, circadian corticosterone release, or the corticosterone response to swim stress. Thus, NE/E projections influence corticosterone secretion only in certain circumstances. They are required for the response to glucoprivation, but are dispensable for circadian activation and for the response to swim stress.

This experiment examined the role of subdiaphragmatic vagal sensory neurons in feeding stimulated by pharmacological blockade of fatty-acid oxidation (lipoprivic feeding) and glucose utilization (glucoprivic feeding). Rats prepared by surgical transection of the subdiaphragmatic vagal trunk or aspiration lesion of the vagal sensory terminal fields in the area postrema-nucleus of the solitary tract (AP-NTS) were maintained and tested on a fat-supplemented, high carbohydrate diet. Fatty-acid oxidation was blocked with mercaptoacetate (MA, 400 and 600 mumol/kg ip) and glucose utilization was blocked with 2-deoxy-D-glucose (2-DG, 100 and 200 mg/kg sc). On test days, rats were injected with MA, 2-DG, or saline, and feeding was measured hourly for 6 h beginning immediately after injection. We found that both subdiaphragmatic vagotomy and AP-NTS lesions abolished lipoprivic feeding. In contrast, glucoprivic feeding was abolished by AP-NTS lesions but not by subdiaphragmatic vagotomy. These results indicate that lipoprivic feeding requires intact subdiaphragmatic vagal sensory neurons that terminate in the AP-NTS region. Glucoprivic feeding is not vagally mediated but also requires a neural substate within the AP-NTS region.