title: Hypothalamic paraventricular 5-hydroxytryptamine inhibits the effects of ghrelin on eating and energy substrate utilization.
abstract: Ghrelin microinjections into discrete regions of the hypothalamus, including the paraventricular nucleus (PVN), stimulate eating and promote carbohydrate oxidation, effects similar to PVN microinjection of neuropeptide Y (NPY). We have also reported that NPY's orexigenic and metabolic effects are antagonized by pretreatment with 5-hydroxytryptamine (5-HT) or 5-HT receptor agonists. In order to determine whether 5-HT also inhibits ghrelin's orexigenic and metabolic actions, the present study examined the effects of 5-HT pretreatment on ghrelin-induced alterations in eating and energy substrate utilization following direct injections into the hypothalamic PVN. Both 5-HT (5-20 nmol) and ghrelin (100 pmol) were administered at the onset of the dark cycle. Food intake was measured 2h postinjection. A separate group of rats (n=8) was injected with 5-HT paired with ghrelin and respiratory quotient (RQ; VCO(2)/VO(2)) was measured over 2h using an open circuit calorimeter. PVN injections of ghrelin increased food intake and increased RQ, reflecting a shift in energy substrate utilization in favor of carbohydrate oxidation. 5-HT effectively blocked the effects of ghrelin on both food intake and RQ. We then administered the 5-HT(2A/2C), receptor agonist, DOI, immediately prior to ghrelin. Similar to 5-HT, PVN DOI blocked ghrelin-induced eating and inhibited the peptide's effect on substrate utilization. These data are in agreement with other evidence suggesting that ghrelin functions as a gut-brain peptide in the control of food intake and energy metabolism, and indicate that 5-HT acts within the PVN to modulate ghrelin's orexigenic and metabolic signaling.
authors.affiliation: Department of Psychology, Reed College, Portland, OR 97202, USA. pcurrie@reed.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Currie
authors.forename: Catherine S
authors.initials: CS
authors.lastname: John
authors.forename: Marjorie L
authors.initials: ML
authors.lastname: Nicholson
authors.forename: Colin D
authors.initials: CD
authors.lastname: Chapman
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Loera
mesh_terms: D000818:Animals; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D054439:Ghrelin / Q000008:administration & dosage* / Q000037:antagonists & inhibitors* / Q000502:physiology; D008297:Male; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000008:administration & dosage*; D013379:Substrate Specificity / Q000187:drug effects / Q000502:physiology
chemical_list: D054439:Ghrelin; D012701:Serotonin