Paraventricular nucleus injections of idazoxan block feeding induced by paraventricular nucleus norepinephrine but not intra-raphe 8-hydroxy-2-(di-n-propylamino)tetralin.
Previous work has shown that injection of the 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the midbrain raphe nuclei activates somatodendritic 5-HT autoreceptors leading to decreased 5-HT synthesis and release in terminal forebrain regions and an increase in feeding behaviour. Since 5-HT is believed to function antagonistically with norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN) to control feeding, it has been proposed that 8-OH-DPAT elicits food intake by removing the inhibitory influence of 5-HT over PVN alpha 2-adrenergic feeding mechanisms. This hypothesis was tested by examining the ability of PVN injection of the alpha 2-adrenoceptor antagonist idazoxan (IDAZ) to attenuate the feeding stimulant action induced by raphe injection of 8-OH-DPAT. In the first series of experiments the dose-response effects of dorsal and median raphe injection of 8-OH-DPAT in addition to PVN NE on feeding were examined. Injection of NE (5-40 nmol) and 8-OH-DPAT (0.4-1.6 nmol) both elicited reliable dose-dependent increases in 1 h food intake compared to saline control. Similar doses of 8-OH-DPAT injected into the PVN failed to alter baseline feeding. A second series of experiments examined the effects of IDAZ on 8-OH-DPAT and NE-stimulated food intake in rats implanted with dorsal or median raphe cannulae as well as cannulae aimed at the PVN.(ABSTRACT TRUNCATED AT 250 WORDS)
Currie
P J
PJ
Section of Biopsychology, Clarke Institute of Psychiatry, Toronto, ON, Canada.
Coscina
D V
DV
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000818:Animals; D004146:Dioxanes / Q000008:administration & dosage; D005247:Feeding Behavior / Q000187:drug effects*; D019329:Idazoxan; D007267:Injections; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D009638:Norepinephrine; D019329:Idazoxan