Cholecystokinin activates catecholaminergic neurons in the caudal medulla that innervate the paraventricular nucleus of the hypothalamus in rats.
Stimulation of gastric vagal afferents by systemic administration of cholecystokinin octapeptide (CCK) inhibits gastric motility, reduces food intake, and stimulates pituitary secretion of oxytocin and adrenocorticotropic hormone in rats. To characterize further the central neural circuits responsible for these effects, the present study used triple-labeling immunocytochemical methods to determine whether or not exogenous CCK activates cFos expression in catecholaminergic neurons in the caudal medulla that project to the paraventricular nucleus of the hypothalamus (PVN). To identify these neurons, the retrograde tracer fluorogold (FG) was iontophoresed into the PVN of anesthetized rats under stereotaxic guidance. After 2 weeks, rats were injected with CCK (100 micrograms/kg, i.p.) and then anesthetized and killed 1 hour later by perfusion fixation. Medullary sections were processed for triple immunocytochemical localization of cFos, retrogradely transported FG, and tyrosine hydroxylase (TH). In rats with FG injections centered in the PVN (n = 10), approximately 70% of the FG-labeled neurons in the caudal nucleus of the solitary tract (NST) and ventrolateral medulla (VLM) expressed cFos. Of these activated PVN-projecting neurons, approximately 78% in the NST and 89% in the VLM were catecholaminergic (TH positive). These results indicate that PVN-projecting catecholaminergic neurons within the caudal medulla are activated by peripheral administration of CCK, further implicating these ascending catecholaminergic pathways in the neuroendocrine, physiological, and behavioral effects produced by gastric vagal stimulation.
Department of Neuroscience, University of Pittsburgh, Pennsylvania 15260, USA.
L
L
Rinaman
G E
GE
Hoffman
J
J
Dohanics
W W
WW
Le
E M
EM
Stricker
J G
JG
Verbalis
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002766:Cholecystokinin / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects
D002395:Catecholamines; D002766:Cholecystokinin