Cholecystokinin, dopamine and glutamate in subcortical and peripheral control of food intake
Author: Qian, Min
Date: 2000-06-09
Location: Hörsalen F51, Huddinge sjukhus
Time: 9.00
Department: Institutionen för klinisk neurovetenskap, arbetsterapi och äldrevårdsforskning (NEUROTEC) / Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC)
Abstract
This thesis analyzes some of the mechanisms whereby cholecystokinin
octapeptide (CCK-8) inhibits food intake in male rats. Depletion of
monoamines using reserpine blocked the capacity for ingestive responses.
These responses were restored in reserpinized rats by treatment with the
non-competitive N-methyl-D-aspartate receptor antagonist MK-801. MK-801
facilitated the intake of an intraorally infused 1M solution of sucrose
and reversed the inhibitory effect of CCK-8. Injection of CCK-8 or intake
of sucrose increased the concentration of dopamine and glutamate in the
nucleus of the solitary tract (NTS), a brainstem relay that transmits
feeding-related information from the gastrointestinal tract to the
forebrain. Binding-sites for CCK-A and CCK-B, dopamine D2, but not D1,
receptor ligands and MK-801 were found in the NTS. These results suggest
that release of dopamine and glutamate in the brainstembrain mediates the
inhibitory effect of CCK-8 on food intake. A full dopamine D1 receptor
agonist caused minor suppression of intraoral intake but a dopamine D2
receptor agonist suppressed intraoral intake when injected into the NTS.
Forebrain dopamine may be redundant in the control of intraoral intake,
because lesioning the ascending dopamdeformitiesinergic pathways by
injection of 6-OHDA into the lateral hypothalamus did not prevent the
animals from showing essentially normal intraoral intake and respond to
CCK-8 by reducing their intake. Lesioning the noradrenergic projections
from the locus coeruleus to the forebrain with the neurotoxin DSP-4
attenuated the intraoral intake of sucrose but did not affect the total
amount of food consumed during a day. Intraoral intake was partially.
restored in DSP-4-treated rats by intracerebroventricular injection of
noradrenaline. Intracerebroventricular injection of neuropeptide Y
inhibited intraoral intake in neurologically intact rats and in
DSP-4-treated rats whose intake had been restored by injection of
noradrenaline. Injection of CCK-8 markedly suppressed intraoral intake,
but binding of [125I]CCK-8 to the NTS was unchanged by the DSP-4
treatment. The noradrenergic innervation of the forebrain may thus be a
substrate which interacts with CCK-8 in the control of meal size.
Infusion of CCK-8 into the hepatic portal vein inhibited intraoral
intake. This effect was blocked by pretreatment with a CCK-A-receptor
antagonist or by hepatic vagal deafferentation. Infusion of MK-801 into
the hepatic portal vein facilitated intraoral intake and this effect was
blocked by hepatic vagotomy. CCK-8 may activate receptors located on
hepatic vagal afferents by a hormonal mechanism and the activity of these
receptors may be modulated by glutamate. It is suggested that CCK and
glutamate interacts both peripherally and centrally in the control of
food intake
List of papers:
I. Bednar I, Qian M, Qureshi GA, Källström L, Johnson AE, Carrer H, Södersten P (1994). "Glutamate inhibits ingestive behaviour" J Neuroendocrinol 6(4): 403-408
Pubmed
II. Qian M, Johnson AE, Källström L, Carrer H, Södersten P (1997). "Cholecystokinin, dopamine D2 and N-methyl-D-aspartate binding sites in the nucleus of the solitary tract of the rat: possible relationship to ingestive behavior" Neuroscience 1077-1089
Pubmed
III. Sederholm F, Qian M, Johnson AE, Södersten P (2000). "Suppression of intraoral intake by dopamine D2 receptor stimulation in male rats" (Manuscript)
IV. Qian M, Johnson AE, Södersten P (1998). "CCK-8 inhibits ingestive behavior in rats with lateral hypothalamic 6-OHDA lesions" Neuroreport 9(12): 2763-2767
Pubmed
V. Qian M, Sederholm F, Johnson AE, Södersten P (2000). "Locus coeruleus noradrenergic lesions attenuate intraoral intake and enhance sensitivity to CCK-8 in rats" (Submitted)
VI. Qian M, Wu GS, Adem A, Johnson AE, Södersten P (1999). "CCK-8 can inhibit ingestive behavior by acting on the liver" Neuroreport 10(2): 359-362
Pubmed
VII. Qian M, Wu GS, Johnson AE, Södersten P (2000). "Evidence that MK801 stimulates intraoral intake by acting on hepatic afferents" (Submitted)
I. Bednar I, Qian M, Qureshi GA, Källström L, Johnson AE, Carrer H, Södersten P (1994). "Glutamate inhibits ingestive behaviour" J Neuroendocrinol 6(4): 403-408
Pubmed
II. Qian M, Johnson AE, Källström L, Carrer H, Södersten P (1997). "Cholecystokinin, dopamine D2 and N-methyl-D-aspartate binding sites in the nucleus of the solitary tract of the rat: possible relationship to ingestive behavior" Neuroscience 1077-1089
Pubmed
III. Sederholm F, Qian M, Johnson AE, Södersten P (2000). "Suppression of intraoral intake by dopamine D2 receptor stimulation in male rats" (Manuscript)
IV. Qian M, Johnson AE, Södersten P (1998). "CCK-8 inhibits ingestive behavior in rats with lateral hypothalamic 6-OHDA lesions" Neuroreport 9(12): 2763-2767
Pubmed
V. Qian M, Sederholm F, Johnson AE, Södersten P (2000). "Locus coeruleus noradrenergic lesions attenuate intraoral intake and enhance sensitivity to CCK-8 in rats" (Submitted)
VI. Qian M, Wu GS, Adem A, Johnson AE, Södersten P (1999). "CCK-8 can inhibit ingestive behavior by acting on the liver" Neuroreport 10(2): 359-362
Pubmed
VII. Qian M, Wu GS, Johnson AE, Södersten P (2000). "Evidence that MK801 stimulates intraoral intake by acting on hepatic afferents" (Submitted)
Issue date: 2000-05-19
Publication year: 2000
ISBN: 91-628-4250-1
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