![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
*
Division of Nutritional Sciences, University of Illinois, Urbana-Champaign, Urbana, IL 61801;
Centre Hospitalier Universitaire Vaudois, Hopital Nestlé, Lausanne, Switzerland; and
**
Department of Animal Sciences, University of Illinois, Urbana-Champaign, Urbana, IL
4To whom correspondence should be addressed. E-mail: beverly1{at}uiuc.edu.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
KEY WORDS: • norepinephrine • neuropeptide Y • microdialysis • push-pull perfusion • zinc deficiency • rats
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
). Rats fed a zinc-deficient diet consume less food and therefore have significantly reduced growth (1
–6
). This reduction in food intake is characterized by a cyclical 3- to 4-d pattern of decreased food consumption (1
–8
). In three-choice macronutrient studies, rats fed zinc-deficient diets preferentially decrease their carbohydrate intake (2
,4
,5
). The changes in intake and selection of zinc-deficient diets have been consistent observations; however, the mechanism for the altered feeding remains unknown.
Within the hypothalamus, the catecholamine neurotransmitter norepinephrine (NE)5
is involved in feeding behavior (9
). The paraventricular nucleus (PVN) is critical for this response because animals with discrete lesions in the PVN had attenuated feeding responses to NE administered intracerebroventricularly (10
). When administered into the PVN, exogenous NE elicits a robust feeding response (11
), mediated by 
2-noradrenergic receptors (12
). Norepinephrine release in the PVN is highest during the onset of the dark phase (13
,14
) when rats are most active and tend to eat their largest meals (15
). Moreover, the onset of the dark phase is also when rats tend to show a preference for carbohydrate consumption (16
). Linking NE release and carbohydrate intake were the reports that a preference for carbohydrates was apparent after injection of NE (11
) or 2-noradrenergic receptor agonists (12
) into the PVN. It was suggested that the decreased intake of rats fed a zinc-deficient diet may be due to increased activity of hypothalamic noradrenergic systems (7
). Although Reeves and O’Dell (7
) found no difference in NE content in the anterior hypothalamus of zinc-deficient rats, Wallwork et al. (8
) reported that brain NE concentrations were higher in rats fed a zinc-deficient diet. There was no correlation between food intake and brain NE content in the latter study; however, the increased food intake in response to NE administered into a lateral ventricle was attenuated in zinc-deficient rats (17
).
A neurotransmitter colocalized with NE in the PVN that also modulates feeding is neuropeptide Y (NPY). Exogenous NPY is a potent orexigenic agent (18
–20
) which, like NE, preferentially increases carbohydrate intake (20
) and has a peak in release at dark onset (21
). During zinc deficiency, hypothalamic NPY mRNA levels and NPY peptide content in the PVN were elevated (3
,6
). However, these data, suggestive of an increase in NPY activity during zinc deficiency, are not consistent with the reduced appetite and selection against carbohydrate by zinc-deficient rats. Because zinc-deficient rats responded to exogenous NPY administration into the PVN, it is unlikely that NPY receptor function or sensitivity is reduced during zinc deficiency (3
).
Because NE and NPY in the PVN influence feeding and carbohydrate selection, the reduced food intake and selection against carbohydrate by rats fed a zinc-deficient diet may be due to alterations in noradrenergic and/or NPY activity in the PVN. The present study evaluated changes in extracellular NE and NPY in the PVN at dark onset in rats fed a zinc-deficient diet. This time frame was selected because of the association between NE and NPY release in the PVN during the initial dark phase with the changes in feeding behavior during zinc deficiency. A series of studies were conducted using microdialysis and push-pull perfusion to monitor NE and NPY, respectively, in chronically zinc-deficient rats. The hypothesis tested was that the changes in feeding behavior during zinc deficiency are due to reduced activity of noradrenergic and NPY systems in the PVN during the initial dark phase.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
225 g) were anesthetized with a cocktail of ketamine HCl/xylazine HCl/acepromazine (30:6:1 mg/kg, intramuscularly). The top of the head was shaved, the skin was cleansed with Providone-Iodine 10% (Betadine), and a 2-cm incision was made. The rat was then placed into a stereotaxic instrument (ASI Instruments, Warren, MI) and a guide cannula positioned to place a microdialysis (Experiment 1) or push-pull (Experiment 2) probe into the PVN: 1.8 mm posterior to bregma, 0.5 mm lateral of midline, and 7.2 mm below dura (22
). Four small stainless steel screws (Small Parts, Miami Beach, FL) and dental acrylic cement fixed the guide cannula in place. Butorphenol analgesia was given postsurgically (0.5 mg/kg, subcutaneously).
Rats were given at least 1 wk to recover from surgery. During this time, they remained on bedding and were fed a diet (Table 1
) containing 10 mg Zn/kg. Rats were then placed into Plexiglas cages with a stainless steel wire bottom 3–4 d before being randomly assigned to one of the three groups, i.e., a zinc-adequate (ZA; 30 mg Zn/kg), zinc-deficient (ZD; 1 mg Zn/kg) or pair-fed (PF) group. Rats in the ZA and ZD groups consumed their diets ad libitum for 14 d. Each pair-fed rat was weight matched to a ZD rat and received the same amount of ZA diet consumed by that rat the day before. Body weights and food intakes were recorded daily. After 14 d, samples of extracellular fluid were collected from the PVN during the transition period from light to dark, i.e., the last hour of the light phase and h 1 of the dark phase. No food was available to the rats during the 2-h sample collection period. All rats were then allowed free access to the ZA diet for 3 d and a second set of samples was collected on d 17 over the same time interval.
|
Experiment 1: effect of zinc deficiency on NE in PVN at dark onset.
Microdialysis probes were made in our laboratory with 1.0 mm of exposed cuprophan membrane (Akzo Nobel, Obernburg, Germany). The relative efficiency of each probe was determined by in vitro recoveries against a standard. To minimize the effects of tissue damage, probes were placed into the PVN 3 h before collecting samples. Samples were collected from unrestrained rats in their home cages using a weighted counterbalance lever with liquid swivel (Instech, Plymouth Meeting, PA). Probes were connected through the swivel to a microinfusion pump (Bioanalytical Systems, West Lafayette, IN) and continuously perfused (1.0 µL/min) with Kreb’s Ringer buffer (147 mmol/L NaCl, 4 mmol/L KCl, 2.4 mmol/L CaCl2; pH, 6.4). Dialysate samples were collected at 20-min intervals for 2 h during the transition from light to dark (1330–1530 h). The 20-µL dialysate samples were collected into microtubes containing 4 µL of 0.1 mol/L HClO4 and immediately frozen to -80°C. Norepinephrine was analyzed by HPLC and electrochemical detection using a Dynamax SD-200 system (Varian Instruments, Woburn, MA) and a 150 x 2 mm C18 reverse-phase column (Keystone Scientific, Bellfonte, PA). The mobile phase was 75 mmol/L NaH2PO4, 1.7 mmol/L 1-octanesulfonic acid, 25 µmol/L Na2EDTA, 8% (v/v) acetonitrile and 0.1% (v/v) diethylamine, (pH = 3.0), at a flow rate of 0.2 mL/min. Norepinephrine was quantified using a DECADE electrochemical detector (Antec Leyden, Leiden, The Netherlands) set at +0.7 V and Dynamax MacIntegrator software. The sensitivity of this protocol for NE was 100 pmol/L.
Experiment 2: effect of zinc deficiency on NPY in PVN at dark onset.
Push-pull probes (Plastics One, Roanoke, VA) were placed into the PVN 3 h before collecting samples to minimize the effects of tissue damage. Probes were connected to a liquid swivel (Instech, Plymouth Meeting, PA) and perfused (5 µL/min) with Kreb’s Ringer buffer (145 mmol/L NaCl, 2.7 mmol/L KCl, 1.0 mmol/L MgCl2; pH, 7.4) containing 0.008% Tween 20 (Polysorbate 20) to prevent sticking of NPY to the walls of the probes and tubing. A Harvard syringe pump (Harvard Apparatus, South Natick, MA) was used for infusion and a CMA/100 microinjection pump (CMA/Microdialysis, North Chelmsford, MA) for withdrawal. Samples were collected at 30-min intervals for 2 h during the transition from light to dark (1400–1600 h). The 150-µL samples were collected into Tygon tubing (Norton Performance Plastics, Akron, OH), transferred into microtubes and immediately frozen to -80°C. NPY was measured using a highly sensitive sandwich ELISA (23
). The detection limit was 0.5 pmol/L and did not cross-react with peptide YY or pancreatic polypeptide.
Statistical analysis.
Body weights, food intake, and extracellular NE or NPY were analyzed by repeated-measures ANOVA. Both the absolute and relative changes in NE or NPY concentrations during the dark phase were analyzed by ANOVA. After a significant ANOVA (P < 0.05), differences among treatments were analyzed by Scheffé’s multiple comparison test. Within treatments, the change in NE or NPY concentrations from baseline was evaluated by paired t test. Results are presented as means ± SEM.
Supplies.
Ketamine, acepromazine, and butorphenol were obtained from Aveco (Fort Dodge, IA). Xylazine was obtained from Vedco, (St. Joseph, MO). All other reagents were purchased from Sigma Chemical (St. Louis, MO). Vitamin and mineral mixes were purchased from Research Diets (New Brunswick, NJ).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Food intakes and body weights of ZD rats were less than those of rats fed the ZA diet (Table 2
). By d 14, body weights of ZD and PF rats were less than that of rats in the ZA group (P = 0.04). On d 14, baseline NE concentrations in the PVN were not different among groups (ZA = 2.1 ± 0.6 nmol/L, ZD = 1.6 ± 0.4 nmol/L, PF = 1.5 ± 0.4 nmol/L). During the first 20 min of the dark period, extracellular NE increased only in the ZA rats to 147 ± 13% of baseline (P < 0.05) (Fig. 1
). The average change during h 1 of the dark phase was higher only in the ZA group (P < 0.01), i.e., 126 ± 3% of baseline for the ZA group, 93 ± 4% of baseline for the ZD group, and 89 ± 10% of baseline for the PF group. After 3 d of repletion or ad libitum consumption (d 14–17), the increase in extracellular NE during h 1 of the dark phase was apparent in all three groups on d 17 (Fig. 2
). Extracellular NE concentration increased to 124 ± 4% of baseline (P < 0.01) in ZA rats, 121 ± 4% of baseline (P < 0.01) in the ZD group and 116 ± 3% of baseline (P = 0.02) in the PF group. The number of rats in each group on d 14 was ZA (n = 5), ZD (n = 8) and PF (n = 5). Complete sample sets were not collected from all rats on d 17 so that the number of rats in each group was ZA (n = 5), ZD (n = 6), and PF (n = 4).
|
|
|
Rats fed the ZD diet consumed less food (P = 0.02) and gained less weight (P < 0.01) than control rats (Table 2)
. Basal concentrations (last hour of light phase) of extracellular NPY in the PVN were 10-fold higher in PF rats on d 14 (P = 0.01), i.e., 7.45 ± 2.01 pmol/L in PF rats compared with 0.58 ± 0.23 pmol/L in ZA rats and 0.72 ± 0.23 pmol/L in ZD rats (Fig. 3
). Despite the higher concentration of extracellular NPY in PF rats, there was no difference among groups in the increase in NPY release during h 1 of the dark phase among groups. During that hour, extracellular NPY increased 174 ± 32% in rats fed ZA (n = 5) (P < 0.01), 144 ± 35% in rats fed ZD (n = 5) diet (P = 0.01) and tended to be higher (101 ± 36%) in PF (n = 6) rats (P = 0.09). After 3 d of ad libitum food consumption, basal concentrations of NPY were normalized in the PF group and extracellular NPY increased during h 1 of the dark to a similar degree in all rats. The number of rats in each group on d 14 was ZA (n = 5), ZD (n = 5) and PF (n = 6). The cannula of several rats became obstructed before and during the second push-pull collection period so that there were 3 rats in each group on d 17. In all rats tested, extracellular NPY concentrations during h 1 of the dark phase were higher than during the last hour of the light phase.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Because the increase in NE was absent in ZD rats, altered noradrenergic activity in the PVN is more likely to contribute to their reduced intake than changes in NPY activity. An increase in NE in the PVN at dark onset influenced feeding behavior (9
), especially the initiation of feeding that occurs at dark onset (14
). When administered into the PVN, exogenous NE elicits a robust feeding response (11
) mediated by 2-noradrenergic receptors (12
). Laboratory rats become active and tend to eat their largest meals at dark onset (15
), and applying exogenous NE into the PVN during the early dark resulted in a larger and longer meal (9
). Rats with selective catecholaminergic lesions in the PVN, induced by 6-hydroxydopamine (6-HDA), consumed less food than control rats, especially during the dark phase (24
). The reduced intake of rats fed a ZD diet (1
–6
) was due to fewer meals and a delay before onset of the first meal during the dark phase (5
). The present results do not support the suggestion by Reeves and O’Dell (7
) that increased activity of hypothalamic noradrenergic systems is responsible for the decreased intake of ZD diets. Although Reeves and O’Dell (7
,25
) found no difference in NE content in the whole brain or the anterior hypothalamus of ZD rats, an earlier study reported that whole-brain NE concentrations tended to be higher in rats fed a ZD diet (8
).
The absence of an increase in NE release in the PVN during the early dark phase is consistent with ZD rats not selecting carbohydrate. Using a three-choice macronutrient system, reduced carbohydrate intake accounted for nearly all of the reduction in food intake by ZD rats (2
,4
), with the lower carbohydrate intake occurring in the early dark phase (5
). Rats tend to prefer carbohydrate during the onset of the dark phase (16
) when NE release in the PVN is higher (13
,14
). The relationship between NE and carbohydrate selection is supported by reports of a preference for carbohydrates after injection of NE (11
) or 2-noradrenergic receptor agonists (12
) into the PVN. Furthermore, reduced NE release in the PVN was suggested to contribute to the decreased intake of carbohydrate after 6-HDA injection (24
).
The lack of an increase in NE at dark onset in the PF control group supports the change in NE being a response to a chronic reduction in food intake and not to zinc deficiency. The absence of an increase in NE in our PF groups is not consistent with restricted rats selecting carbohydrate. However, the results are consistent with macronutrient selection studies showing that rats restricted (food deprived) for 24 h tend to select fat (26
). In the present study, PF rats generally ate their ration within the first 2 or 3 h of presentation and were likely to have been deprived of food for 20–23 h at the time of sample collection. Lax et al. (27
) reported a difference in the feeding response of rats on d 1 of a short-term food deprivation vs. after dietary restriction for 15 d. When we measured extracellular NE in the PVN of rats after a single 23-h period of food deprivation, NE concentrations tended to be higher (P = 0.06) in restricted rats (6.2 ± 1.9 nmol/L) than in controls (2.3 ± 0.8 nmol/L) (28
). It is possible that basal NE concentrations of PF rats, and perhaps rats fed the ZD diet, were higher during the initial portion of the study. The return of basal extracellular NE concentrations in the PVN to normal levels (i.e., the same as ZA rats) may reflect adaptation to chronic food restriction.
The increased expression of NPY, seen as an increase in NPY mRNA in the arcuate nucleus (ARC) and NPY peptide in the PVN in ZD rats (3
,6
), is apparently not translated to increased release in the PVN. The higher basal concentration of NPY in the PVN of PF rats is consistent with the observation that the rate of NPY synthesis in the ARC and transport into the PVN are increased by food deprivation (29
). Both baseline (e.g., last hour of light) NPY levels and the increase in NPY during the dark were the same in ZA and ZD rats. Because food intakes were quite different for these two groups of rats, it appears that the amount of food consumed is not dependent on NPY levels. Data from NPY knockout mice are consistent with this interpretation. Although NPY is a potent stimulator of feeding (18
,19
), food intake, body weight and adiposity were normal in NPY-deficient mice (30
). In the PVN, NPY has also been implicated in stimulating food intake at dark onset and promoting carbohydrate consumption (11
,19
,26
). During zinc deficiency, NPY levels and release in the PVN are the same as those of control rats yet carbohydrate intake is reduced (2
,4
,5
).
The increase in basal NPY concentration in PF rats was not due to the lower level of food intake per se. Rats in the PF group received the same amount of food as rats in the ZD group, yet basal extracellular levels of NPY were 10 times higher and still increased in h 1 of dark to the same degree as the controls. The elevated NPY concentration in the PF group after 14 d and its return to control after ad libitum food consumption are consistent with the literature. Food deprivation resulted in an accumulation of NPY peptide in the PVN, which returned to the control levels after feeding (31
). Similarly, NPY release in the PVN, measured by push-pull perfusion, increased threefold after 3 d of food deprivation and returned to normal within 24 h of refeeding (32
). The lack of an increase in basal NPY in ZD rats would be expected to reduce their "drive" to eat. During the repletion phase, d 14–17, PF rats consumed more food sooner than did ZD rats fed the ZA diet. Whether this difference is due to the elevated basal NPY levels in the PVN of PF rats is unknown.
Because NE is often colocalized with NPY, it is likely that there is a functional interaction between NE and NPY within the PVN. NPY-induced feeding is independent of NE in the PVN (33
). The expression of NPY in noradrenergic neurons providing input to the PVN appears to be limited to a subpopulation of cells from the A1 group, with 60% of the cells labeling for both NE and NPY (34
). We are unaware of any report that differentiates the NPY response in the PVN among neurons arising from hypothalamic and hindbrain sites. It is possible that the increase in NPY from the ARC was offset by reduced NPY from the hindbrain. This possibility is consistent with the lack of increase in NE during the dark phase and previous data documenting increased NPY message in the ARC (3
,6
). However, this argument does not explain why the NE response was the same in PF and ZD rats.
In summary, at the onset of the dark phase, rats fed a ZD diet had a different profile of neurotransmitter release in the PVN. In control rats, both NE and NPY release increased during h 1 of the dark phase. In ZD rats, the increase in extracellular NE was absent and the increase in NPY was similar to that of control rats. However, the increase in extracellular NE in the PVN was also absent in non-ZD rats fed the same amount of food as ZD rats. Although the disturbance in the noradrenergic system in the PVN may be involved in the reduction of food intake in general, and carbohydrate consumption in particular, in rats fed a ZD diet, the results from the PF controls suggest that this may result from reduced food intake rather than a change in zinc status. There was no apparent effect of zinc deficiency on basal levels of NPY or peak NPY release at dark onset. However, the elevated baseline level of NPY in PF rats was not evident in the ZD rats consuming the same amount of food. We have no evidence that NPY processing was affected in rats fed the ZD diet. The increase in NPY mRNA and peptide content, similar to restricted rats, is consistent with the NPY system of ZD rats being responsive to signals of energy deficit. Why the increase in NPY content is not translated to increased release is unclear. Zinc deficiency affects noradrenergic and NPY activity in the PVN at dark onset. It is unclear whether the changes in these neural systems are responsible for the altered feeding behavior accompanying zinc deficiency.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
2 Present address: Department of Animal Sciences, University of Missouri, Columbia, MO 65211.
3 Present address: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556 .
5 Abbreviations used: ARC, arcuate nucleus; 6-HDA, 6-hydroxydopamine; NE, norepinephrine; NYP, neuropeptide Y; PF, pair-fed; PVN, paraventricular nucleus; ZA, zinc-adequate; ZD, zinc-deficient.
Manuscript received 13 April 2001. Initial review completed 26 June 2001. Revision accepted 26 October 2001.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Chesters, J. K. & Quarterman, J. (1970) Effects of zinc deficiency on food intake and feeding patterns of rats. Br. J. Nutr. 24:1061-1069.[Medline]
2.
Kennedy, K. J., Rains, T. M. & Shay, N. F. (1998) Zinc deficiency changes preferred macronutrient intake in subpopulations of Sprague-Dawley outbred rats and reduces hepatic pyruvate kinase gene expression. J. Nutr. 128:43-49.
3.
Lee, R. G., Rains, T. M., Tovar-Palacio, C., Beverly, J. L. & Shay, N. F. (1998) Zinc deficiency increases hypothalamic neuropeptide Y and neuropeptide Y mRNA levels and does not block neuropeptide Y-induced feeding in rats. J. Nutr. 128:1218-1223.
4. Rains, T. M. & Shay, N. F. (1995) Zinc status specifically changes preferences for carbohydrate and protein in rats selecting from separate carbohydrate-, protein- and fat-containing diets. J. Nutr. 125:2874-2879.
5. Rains, T. M., Hedrick, S., Randall, A. C., Lee, R. G., Kennedy, K. J. & Shay, N. F. (1998) Food intake patterns are altered during long-term zinc deficiency in rats. Physiol. Behav. 65:473-478.[Medline]
6. Selvais, P. L., Labuche, C., Nguyen, X. N., Ketelslegers, J. M., Denef, J. F. & Maiter, D. M. (1997) Cyclic feeding behaviour and changes in hypothalamic galanin and neuropeptide Y gene expression induced by zinc deficiency in the rat. J. Neuroendocrinol. 9:55-62.[Medline]
7. Reeves, P. G. & O’Dell, B. L. (1984) The effect of dietary tyrosine levels on food intake in zinc-deficient rats. J. Nutr. 114:761-767.
8. Wallwork, J. C., Botnen, J. H. & Sandstead, H. H. (1982) Influence of dietary zinc on rat brain catecholamines. J. Nutr. 112:514-519.
9. Shor-Posner, G., Grinker, J. A., Marinescu, C. & Leibowitz, S. F. (1985) Role of hypothalamic norepinephrine in control of meal patterns. Physiol. Behav. 35:209-214.[Medline]
10. Leibowitz, S. F., Hammer, N. J. & Chang, K. (1983) Feeding behavior induced by central norepinephrine injection is attenuated by discrete lesions in the hypothalamic paraventricular nucleus. Pharmacol. Biochem. Behav. 19:945-950.[Medline]
11. Tempel, D. L. & Leibowitz, S. F. (1990) Diurnal variations in the feeding responses to norepinephrine, neuropeptide Y and galanin in the PVN. Brain Res. Bull. 25:821-825.[Medline]
12. Currie, P. J. & Wilson, L. M. (1992) Yohimbine attenuates clonidine-induced feeding and macronutrient selection in genetically obese (ob/ob) mice. Pharmacol. Biochem. Behav. 43:1039-1046.[Medline]
13. Paez, X., Stanley, B. G. & Leibowitz, S. F. (1993) Microdialysis analysis of norepinephrine levels in the paraventricular nucleus in association with food intake at dark onset. Brain Res 606:167-170.[Medline]
14. Stanley, B. G., Schwartz, D. H., Hernandez, L., Hoebel, B. G. & Leibowitz, S. F. (1989) Patterns of extracellular norepinephrine in the paraventricular hypothalamus: relationship to circadian rhythm and deprivation-induced eating behavior. Life Sci 45:275-282.[Medline]
15. Strubbe, J. H., Keyser, J., Dijkstra, T. & Prins, A. J. (1986) Interaction between circadian and caloric control of feeding behavior in the rat. Physiol. Behav. 36:489-493.[Medline]
16.
Tempel, D. L., Shor-Posner, G., Dwyer, D. & Leibowitz, S. F. (1989) Nocturnal patterns of macronutrient intake in freely feeding and food-deprived rats. Am. J. Physiol. 256:R541-R548.
17. Essatara, M. B., McClain, C. J., Levine, A. S. & Morley, J. E. (1984) Zinc deficiency and anorexia in rats: the effect of central administration of norepinephrine, muscimol and bromerogocryptine. Physiol. Behav. 32:479-482.[Medline]
18. Clark, J. T., Kalra, P. S. & Kalra, S. P. (1985) Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats. Endocrinology 117:2435-2442.[Abstract]
19.
Stanley, B. G. & Leibowitz, S. F. (1985) Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. Proc. Natl. Acad. Sci U.S.A. 82:3940-3943.
20. Stanley, B. G., Daniel, D. R., Chin, A. S. & Leibowitz, S. F. (1985) Paraventricular nucleus injections of peptide YY and neuropeptide Y preferentially enhance carbohydrate ingestion. Peptides 6:1205-1211.[Medline]
21. Jhanwar-Uniyal, M., Beck, B., Burlet, C. & Leibowitz, S. F. (1990) Diurnal rhythm of neuropeptide Y-like immunoreactivity in the suprachiasmatic, arcuate and paraventricular nuclei and other hypothalamic sites. Brain Res 536:331-334.[Medline]
22. Paxinos, G. & Watson, C. (1986) The Rat Brain in Stereotaxic Coordinates 2nd ed. 1986 Academic Press Orlando, FL. .
23. Grouzmann, E., Aubert, J. F., Waeber, B. & Brunner, H. R. (1992) A sensitive and specific two-site, sandwich-amplified enzyme immunoassay for neuropeptide Y. Peptides 13:1049-1054.[Medline]
24. Shor-Posner, G., Azar, A. P., Jhanwar-Uniyal, M., Filart, R. & Leibowitz, S. F. (1986) Destruction of noradrenergic innervation to the paraventricular nucleus: deficits in food intake, macronutrient selection, and compensatory eating after food deprivation. Pharmacol. Biochem. Behav. 25:381-392.[Medline]
25. Reeves, P. G. & O’Dell, B. L. (1981) Short-term zinc deficiency in the rat and self-section of dietary protein level. J. Nutr. 111:375-383.
26.
Welch, C. C., Grace, M. K., Billington, C. J. & Levine, A. S. (1994) Preference and diet type affect macronutrient selection after morphine, NPY, norepinephrine, and deprivation. Am. J. Physiol 266:R426-R433.
27. Lax, P., Larue-Achagiotis, C., Martel, P., Madrid, J. A. & Verger, P. (1998) Repeated short-fasting modifies the macronutrient self-selection pattern in rats. Physiol. Behav. 65:69-76.[Medline]
28. Huntington, C. H. (2000) Effect of Zinc Status on Neurotransmitter Activity in the Paraventricular Nucleus at Dark Onset in Rats 2000 Doctoral thesis University of Illinois, Urbana, IL. .
29. Sahu, A., Kalra, S. P., Crowley, W. R. & Kalra, P. S. (1988) Evidence that NPY-containing neurons in the brainstem project into selected hypothalamic nuclei: implication in feeding behavior. Brain Res 457:376-378.[Medline]
30.
Erickson, J. C., Hollopeter, G. & Palmiter, R. D. (1996) Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y [see comments]. Science (Washington DC) 274:1704-1707.
31. Sahu, A., Kalra, P. S. & Kalra, S. P. (1988) Food deprivation and ingestion induce reciprocal changes in neuropeptide Y concentrations in the paraventricular nucleus. Peptides 9:83-86.[Medline]
32.
Kalra, S. P., Dube, M. G., Sahu, A., Phelps, C. P. & Kalra, P. S. (1991) Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food. Proc. Natl. Acad. Sci. U.S.A. 88:10931-10935.
33. Kyrkouli, S. E., Stanley, B. G. & Leibowitz, S. F. (1992) Differential effects of galanin and neuropeptide Y on extracellular norepinephrine levels in the paraventricular hypothalamic nucleus of the rat: a microdialysis study. Life Sci 51:203-210.[Medline]
34. Sawchenko, P. E., Swanson, L. W., Grzanna, R., Howe, P. R., Bloom, S. R. & Polak, J. M. (1985) Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J. Comp. Neurol. 241:138-153.[Medline]
35. Reeves, P. G., Nielsen, F. H. & Fahey, G. C., Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J. Nutr. 123:1939-1951.
This article has been cited by other articles:
|
|
 |
|
  H. M. Lehmann, B. B. Brothwell, L. P. Volak, and D. J. Bobilya Zinc Status Influences Zinc Transport by Porcine Brain Capillary Endothelial Cells J. Nutr., September 1, 2002; 132(9): 2763 - 2768. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
