Clonidine hyperphagia: neuroanatomic substrates and specific function.
Recent studies have indicated that the alpha 2-noradrenergic agonist clonidine (CLON), when peripherally and centrally administered, potentiates feeding in satiated rats in a manner similar to that observed following injection of norepinephrine (NE) into the hypothalamic paraventricular nucleus (PVN). The present experiments examined the effects of CLON on meal patterns and macronutrient selection and compared these findings to earlier NE-stimulated feeding studies. Administration of CLON (25 nmoles), directly into the PVN (n = 5), similar to PVN injected NE, produced an increase in meal size (190%) and feeding duration (164%), with no change in meal frequency. Additional tests were conducted in rats with PVN electrolytic or 6-hydroxydopamine lesions. In Sham rats (n = 16) peripheral CLON (0.05 mg/kg), like NE, produced an increase in food intake and particularly potentiated carbohydrate ingestion. Discrete electrolytic lesions of the PVN (n = 5) abolished this CLON-induced feeding and carbohydrate preference, suggesting that the PVN may be a primary site for CLON-stimulated hyperphagia. Neurotoxin lesions of the PVN (n = 17), which reduced PVN NE levels by 75%, failed to alter peripheral CLON-induced feeding. This and other evidence indicates that this agonist may be acting via postsynaptic alpha 2 receptors in the PVN to potentiate carbohydrate intake, rather than via presynaptic release of NE from nerve endings in the PVN.
Shor-Posner
G
G
Rockefeller University, New York, NY 10021.
Azar
A P
AP
Volpe
M
M
Grinker
J A
JA
Leibowitz
S F
SF
D000818:Animals; D002395:Catecholamines / Q000032:analysis; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D006892:Hydroxydopamines / Q000494:pharmacology; D007267:Injections; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D016627:Oxidopamine; D010286:Paraventricular Hypothalamic Nucleus / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D002395:Catecholamines; D006892:Hydroxydopamines; D016627:Oxidopamine; D003000:Clonidine; D009638:Norepinephrine