Hindbrain noradrenergic lesions attenuate anorexia and alter central cFos expression in rats after gastric viscerosensory stimulation.

Behavioral, autonomic, and endocrine outputs of the CNS are subject to important feedback modulation by viscerosensory signals that are conveyed initially to the hindbrain nucleus of the solitary tract (NST). In the present study, noradrenergic (NA) neurons [i.e., those that express the NA synthetic enzyme dopamine beta hydroxylase (DbH)] in the caudal NST were lesioned to determine their role in mediating anorexic responses to gastric stimulation and in conveying gastric sensory signals to the hypothalamus and amygdala. For this purpose, saporin toxin conjugated to an antibody against DbH was microinjected bilaterally into the caudal NST in adult rats. Control rats received similar microinjections of vehicle. Several weeks later, rats were tested for the ability of systemic cholecystokinin octapeptide (CCK) (0 or 10 microg/kg) to inhibit food intake. CCK-induced anorexia was significantly attenuated in toxin-treated rats. Rats subsequently were used in a terminal cFos study to determine central neural activation patterns after systemic CCK or vehicle and to evaluate lesion extent. Toxin-induced loss of DbH-positive NST neurons was positively correlated with loss of CCK-induced anorexia. Hypothalamic cFos expression was markedly attenuated in lesioned rats after CCK treatment, whereas CCK-induced neural activation in the parabrachial nucleus and amygdala appeared normal. These findings suggest that hindbrain NA neurons are an integral component of brainstem circuits that mediate CCK-induced anorexia and also are necessary for hypothalamic but not parabrachial or amygdala responses to gastric sensory stimulation.