Evidence of an orexigenic role for cocaine- and amphetamine-regulated transcript after administration into discrete hypothalamic nuclei.
Cocaine- and amphetamine-regulated transcript is expressed in hypothalamic regions involved in the central control of food intake. Previous data have implicated cocaine- and amphetamine-regulated transcript as an anorectic peptide. We studied the effect of the active fragment of cocaine- and amphetamine-regulated transcript, cocaine- and amphetamine-regulated transcript-(55-102), on feeding when injected into discrete nuclei of the hypothalamus. Cocaine- and amphetamine-regulated transcript-(55-102) (0.04 nmol) elicited a delayed, but significant, increase in feeding in 24-h fasted rats after injection into the ventromedial nucleus (1-2 h, 261 +/- 60% of control; P < 0.05) and arcuate nucleus (1-2 h, 225 +/- 38% of control; P < 0.05) of the hypothalamus. Administration of a higher dose of cocaine- and amphetamine-regulated transcript-(55-102) (0.2 nmol) elicited a significant increase in feeding after injection into the ventromedial nucleus (1-2 h, 1253 +/- 179% of control; P < 0.001), arcuate nucleus (1-2 h, 265 +/- 43% of control; P < 0.05), paraventricular nucleus (2-4 h food intake, 186 +/- 29% of control; P < 0.05), lateral hypothalamic area (2-4 h, 280 +/- 34% of control; P < 0.001), anterior hypothalamic area (2-4 h, 252 +/- 42% of control; P < 0.01), dorsomedial nucleus (2-4 h, 368 +/- 29% of control;P < 0.001) and supraoptic nucleus (2-4 h, 212 +/- 34% of control; P < 0.05) of the hypothalamus. Administration of cocaine- and amphetamine-regulated transcript-(55-102) into the third ventricle of the hypothalamus resulted in an inhibition in feeding [0-4 h (0.4 nmol), 33 +/- 13% control; P < 0.001], but was associated with marked abnormalities in behavior, which may have interfered with feeding. These behavioral abnormalities were not observed after the administration of cocaine- and amphetamine-regulated transcript-(55-102) directly into the arcuate nucleus. These data suggest that cocaine- and amphetamine-regulated transcript may play an orexigenic role in the hypothalamic feeding circuitry.
Abbott
C R
CR
Endocrine Unit, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom W12 ONN.
Rossi
M
M
Wren
A M
AM
Murphy
K G
KG
Kennedy
A R
AR
Stanley
S A
SA
Zollner
A N
AN
Morgan
D G
DG
Morgan
I
I
Ghatei
M A
MA
Small
C J
CJ
Bloom
S R
SR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis*; D004435:Eating / Q000187:drug effects; D005215:Fasting / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007267:Injections; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009419:Nerve Tissue Proteins; D009479:Neuropeptides / Q000096:biosynthesis*; D000068797:Orexins; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012528:Satiety Response / Q000502:physiology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000068797:Orexins; D010446:Peptide Fragments; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein