Nocistatin inhibits food intake in rats.
Nocistatin, a product of the same precursor as nociceptin/orphanin FQ (N/OFQ), has been shown to antagonize effects of N/OFQ. N/OFQ stimulates feeding, most probably by inhibiting activation of neurons containing oxytocin (OT) and vasopressin (VP), peptides considered as satiety factors, and implicated in the development of conditioned taste aversion (CTA). The present study was designed to investigate whether intracerebroventricularly (ICV) injected nocistatin (a) affects deprivation- and N/OFQ-induced feeding, (b) causes CTA, and (c) induces activation of hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, as well as OT and VP neurons present in these regions. C-Fos immunohistochemistry was used as a marker of cellular activation. Nocistatin (1-3 nmol) significantly reduced food intake in deprived rats during the first and second hour post-injection. Doses of 1-3 nmol suppressed N/OFQ-induced feeding. Nocistatin at the highest (3 nmol) dose did not cause CTA. It also did not affect activation of the PVN or SON. In nocistatin-treated animals, the percentage of Fos-positive OT and VP neurons was similar to controls. We conclude that nocistatin antagonizes the influence of N/OFQ on feeding and suppresses deprivation-induced food consumption through mechanisms other than aversion. Nocistatin does not, however, activate the PVN or SON. It does not exert its effects via VP or OT neurons.
Minnesota Obesity Center, Research Service 151, Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417, USA.
P K
PK
Olszewski
T J
TJ
Shaw
M K
MK
Grace
C J
CJ
Billington
A S
AS
Levine
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D018846:Excitatory Amino Acids / Q000819:agonists; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism; D013649:Taste / Q000187:drug effects; D014667:Vasopressins / Q000378:metabolism; D000097629:Nociceptin
D000701:Analgesics, Opioid; D018846:Excitatory Amino Acids; D018847:Opioid Peptides; D010121:Oxytocin; D016760:Proto-Oncogene Proteins c-fos; D014667:Vasopressins; D000097629:Nociceptin; C111148:nocistatin