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Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Address all correspondence and requests for reprints to: Diana L. Williams, Department of Psychology, University of Pennsylvania, 3815 Walnut Street, Philadelphia, Pennsylvania 19104. E-mail: dianaw{at}psych.upenn.edu
Fourth intracerebroventricular (4th-icv) administration of the
melanocortin-3/4 receptor (MC3/4-R) agonist, MTII, reduces food intake;
the antagonist, SHU9119, increases feeding. The dorsal motor nucleus of
the vagus nerve (DMX) contains the highest density of MC4-R messenger
RNA in the brain. To explore the possibility that the DMX contributes
to 4th-icv MC4-R effects, we delivered doses of MTII and SHU9119 that
are subthreshold for ventricular response unilaterally through a
cannula centered above the DMX. MTII markedly suppressed 2-h (50%),
4-h (50%), and 24-h (33%) intake. Feeding was significantly increased
4 h (50%) and 24 h (20%) after SHU9119 injections. These
results suggest that receptors in the DMX, or the dorsal vagal complex
more generally, underlie effects obtained with 4th-icv administration
of these ligands. We investigated possible vagal mediation of 4th-icv
MTII effects by giving the agonist to rats with subdiaphragmatic
vagotomy. MTII suppressed 2-, 4-, and 24-h liquid diet intake (
80%)
to the same extent in vagotomized and surgical control rats. We
conclude that stimulation or antagonism of MC3/4-Rs in the dorsal vagal
complex yields effects on food intake that do not require an intact
vagus nerve.
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