TY - JOUR
T1 - Evidence of an orexigenic role for cocaine- and amphetamine-regulated transcript after administration into discrete hypothalamic nuclei
AU - Abbott, C. R.
AU - Rossi, M.
AU - Wren, A. M.
AU - Murphy, K. G.
AU - Kennedy, A. R.
AU - Stanley, S. A.
AU - Zollner, A. N.
AU - Morgan, D. G.A.
AU - Morgan, I.
AU - Ghatei, M. A.
AU - Small, C. J.
AU - Bloom, S. R.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/17844380766
U2 - 10.1210/endo.142.8.8304
DO - 10.1210/endo.142.8.8304
M3 - Article
C2 - 11459791
AN - SCOPUS:17844380766
SN - 0013-7227
VL - 142
SP - 3457
EP - 3463
JO - Endocrinology
JF - Endocrinology
IS - 8
ER -