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Am J Physiol Regul Integr Comp Physiol 275: R471-R477, 1998;
0363-6119/98 $5.00
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Vol. 275, Issue 2, R471-R477, August 1998

Divergence of the feeding and thermogenic pathways influenced by NPY in the hypothalamic PVN of the rat

Catherine M. Kotz1,2, Jacqueline E. Briggs2, Martha K. Grace3, Allen S. Levine1,2,3,4, and Charles J. Billington2,3

Departments of 1 Food Science and Nutrition, 4 Psychiatry, and 2 Medicine, University of Minnesota, Saint Paul 55108, and 3 Veterans Affairs Medical Center, Minneapolis, Minnesota 55417

    ABSTRACT
Top
Abstract
Introduction
Methods
Results
Discussion
References

Neuropeptide Y (NPY) injected into the paraventricular nucleus (PVN) increases feeding and decreases brown adipose tissue (BAT) uncoupling protein (UCP) and lipoprotein lipase (LPL) mRNA. Previously we reported that the feeding and BAT effects induced by NPY in the PVN are blocked by 50 µg naltrexone (NTX) in the rostral nucleus of the solitary tract (rNTS). We sought to determine whether the effect of rNTS NTX on PVN NPY-induced alterations in energy metabolism occurred at lower doses of NTX. Male Sprague-Dawley rats were fitted with cannulas into two sites: PVN and rNTS. Feeding response, BAT UCP, and LPL mRNA were measured after injection of 0, 5, 10, and 25 µg NTX in the rNTS ± 1 µg NPY in the PVN. One-hour feeding response to PVN NPY was significantly and dose dependently decreased by 10 and 25 µg rNTS NTX (-23 and -31%, respectively). However, rNTS NTX did not block the PVN NPY-induced decrease in BAT UCP or LPL mRNA. BAT beta -actin mRNA (as a measure of overall changes in gene expression) was unchanged among treatment groups. These results indicate a possible divergence in the PVN NPY feeding-stimulatory/BAT-inhibitory pathway, such that PVN NPY feeding effects may be routed through the rNTS whereas BAT effects may be due to alterations at another neural site.

nucleus of the solitary tract; opioids; feeding behavior; brown adipose tissue; uncoupling protein

    INTRODUCTION
Top
Abstract
Introduction
Methods
Results
Discussion
References

NEUROPEPTIDE Y (NPY) administered in the paraventricular nucleus (PVN) increases feeding (8, 24, 33), decreases brown adipose tissue (BAT) thermogenesis, and increases energy storage in white fat (4, 5). Although NPY is produced and acts at other central sites (2), injection of NPY in the PVN and the closely associated perifornical nucleus results in the largest increase in feeding (5, 34), and this is the only specific site in which the effect of NPY administration on brown and white adipose tissue has been tested (5). These effects of NPY administered in PVN, increased feeding, decreased BAT activity, and increased energy storage in white fat, produce positive energy balance, and animals chronically injected with NPY become obese (32).

Peripheral and central [intracerebroventricular, rostral nucleus of the solitary tract (rNTS), and central nucleus of the amygdala] administration of opioid antagonists decrease NPY-induced feeding (11, 17, 18, 20, 21, 23, 24, 30), indicating that NPY interacts with the opioid system in the regulation of food intake. Opioids have a well-established role in feeding (13), and NPY-opioid interactions have been reported in several situations. Peripheral opioid agonists decrease, and antagonists increase, NPY mRNA and peptide levels, indicating a possible feedback system monitoring NPY-opioid interaction (6, 19, 22, 27, 29).

Recently, we found that naltrexone (NTX) administered in the rNTS blocked feeding produced by NPY given into the PVN, whereas the same dose of PVN NTX did not block PVN NPY-induced feeding (18), suggesting that NPY relies on functional opioid pathways in the rNTS for feeding stimulation. The NTS contains a high density of opioid receptors (25) and all three families of opioid peptides (1), and opioids in the rNTS have been shown to stimulate feeding (16). The rNTS receives first-order neuronal projections conveying gustatory and somesthetic sensations from the tongue and mouth, and the caudal NTS receives visceral afferent information from vagal and glossopharyngeal nerves (3). The NTS has neural connections with almost all brain regions involved in nutrient homeostasis, allowing for integration of nutrient information and signals related to energy balance (3). Lesioning PVN-NTS neural connections and the area postrema with surrounding NTS results in alteration of feeding behavior (9, 10, 14, 31).

The current study was designed to further characterize the link between PVN NPY and opioid receptor activity in the rNTS. Because of the relatively high dose of NTX used in our previous studies (50 µg repeatedly), we set out to determine the lowest effective dose of NTX in the rNTS on PVN NPY administration effects on feeding and BAT activity. BAT uncoupling protein (UCP) and lipoprotein lipase (LPL) mRNA levels were measured as indicators of BAT thermogenic activity. beta -Actin mRNA was measured to rule out nonspecific changes in gene expression due to treatment.

    METHODS
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Abstract
Introduction
Methods
Results
Discussion
References

Animals

Male Sprague-Dawley rats (Harlan, Madison, WI) weighing 250-350 g were individually housed in conventional hanging cages with a 12:12-h light-dark photoperiod (lights on at 0700) in a temperature-controlled room (21-22°C). Purina verified lab chow and water were allowed ad libitum, except where noted.

Cannulation

Rats were anesthetized with Nembutal (40 mg/kg) and fitted with 26-gauge stainless steel guide cannulas (Plastics One, Austin, TX) placed into the rNTS at the rostral extent of the nucleus ambiguus and into the PVN for experiments 1 and 2. Stereotaxic coordinates were determined from the rat brain atlas of Paxinos and Watson (28) and were as follows: PVN: 0.5 mm lateral, 1.9 mm posterior to bregma, and 7.3 mm below the skull surface; rNTS: 2.0 mm lateral, 2.6 mm posterior to the interaural line, and 7.2 mm below the skull surface. For all cannulations, the incisor bar was set at 3.3 mm below the ear bars. Representative photomicrographs of correctly placed PVN and rNTS cannulas are illustrated in Fig. 1. At least 7 days elapsed after surgery before experimental trials.


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  		Fig. 1.   Photograph of histological preparations of coronal sections illustrating typical paraventricular nucleus (PVN; A) and rostral nucleus of the solitary tract (rNTS; B) cannula placements. CT, cannula tract; 3V, third ventricle; MVe, ventral medial vestibular nuclei. Scale bar, 150 µm; magnification ×10.

Injections

Injections into the PVN and the rNTS were given in a 1-µl volume over 30 s by the use of a 33-gauge internal cannula (Plastics One). Injections into the rNTS were given just before PVN injections, with at least a 60-s delay between injections. The injector extended 1 mm beyond the end of the guide cannula.

Verification of Cannula Placement

After both experiments, brains were dissected out and stored in a 10% formaldehyde solution for later placement verification by histological examination. Representative photographs of coronal sections through the PVN and the rNTS demonstrating cannulas correctly placed within these regions are shown in Fig. 1. Data from animals with incorrectly placed cannulas were excluded from the final analysis; in study 1, four rats were excluded, and in study 2, seven rats were excluded. Data from animals with incorrectly placed cannulas were analyzed in an attempt to confirm specificity of effects observed to the rNTS.

Drugs

NTX was purchased from Research Biochemicals International (Natick, MA). Porcine NPY was purchased from Peninsula Laboratories (Belmont, CA). All drugs were dissolved in 0.9% saline just before use.

Food Intake Measurements

Food was allowed ad libitum until the start of each experimental trial. Just before injection, food was removed, and immediately after injection, preweighed pellets of chow were placed inside the rat cage. At selected time points, pellets and spillage were weighed and subtracted from the initial weight to quantify the amount of food eaten.

UCP, LPL, and beta -Actin mRNA Determination

In expt 2, rats were killed by decapitation 1-2 h after the final set of NTX and NPY injections, and interscapular brown fat was dissected free from surrounding tissue. Total RNA from brown fat was extracted by the rapid guanidine thiocyanate-phenol-chloroform method (7). Tissue was homogenized in a buffer containing 4 M guanidine thiocyanate with added beta -mercaptoethanol and water-saturated molecular biology-grade phenol. Sarcosyl, 2 M sodium acetate, and chloroform were then added. After centrifugation, the aqueous phase was precipitated with isopropanol, resuspended in guanidine thiocyanate buffer, and reprecipitated with isopropanol. The pellet was washed with 75% ethanol. The resulting RNA was stored in 100% ethanol at -80°C.

Samples were analyzed by the slot-blot method using nylon membranes (Zeta-Probe; Bio-Rad, Hercules, CA). Aliquots of total RNA were dissolved in 7.4% formaldehyde:6× SSC (1× SSC = 0.15 M NaCl, 0.015 M sodium citrate) and denatured for 10 min at 68°C. Two micrograms of total RNA from each sample were slotted onto a 6× SSC-soaked nylon membrane (Zeta-Probe, Bio-Rad). The membranes were then placed under ultraviolet (UV) light, and even loading of samples was verified by shadowing of the nucleic acids (35). A photograph of the shadowed membrane was taken, scanned using an image scanner (UMAX), and quantified by 2-D densitometry. The coefficient of variation (r2) for the RNA loading of the BAT RNA slot blot was 0.028. The RNA was fixed onto the nylon after air drying by UV cross-linking. The slot-blot membranes were prehybridized for 24 h at 42°C in 50% formamide, 5× SSC, 10× Denhardt's solution, 0.1% SDS, and denatured salmon sperm DNA in 50 mM Na phosphate, pH 6.5. For the UCP hybridization, we used a UCP 365 probe, generously supplied by Dr. Daniel Ricquier (Meudon, France). For the LPL hybridization, we used an LPL probe, generously supplied by Dr. Robert Eckel (Denver, CO). For the beta -actin hybridization, we used a beta -actin probe obtained from ONCOR (Gaithersburg, MD). The hybridization medium (16 ml per tube) was 50% formamide, 5× SSC, 2× Denhardt's solution, 0.2% SDS, denatured salmon sperm DNA, and yeast tRNA in 50 mM Na phosphate, pH 6.5, with the addition of 106 counts · min-1 · ml-1 of [32P]dCTP (specific activity = 3,000 Ci/mmol) random primer labeled probe. After hybridization for 24 h at 42°C, the nylon membranes were subjected to high- and low-salt washing and then placed in a cassette with Kodak XAR film for autoradiography in a -70°C freezer. After sufficient time (>6 mo) to allow for the [32P] signal to deteriorate, the membranes were reloaded in cassettes and exposed to film. After it was determined that the autoradiograms were negative for [32P] signal, the membranes were subsequently labeled with beta -actin (24 h at 42°C). Once the autoradiograms were developed, samples were quantified by 2-D densitometry (Bio-Rad) and mRNA levels expressed in optical density units. To normalize our data for overall changes in gene expression and minor individual variability in RNA loading onto the slot blots, UCP mRNA and LPL mRNA levels were divided by beta -actin mRNA levels such that data is expressed as UCP mRNA/beta -actin mRNA and LPL mRNA/beta -actin mRNA, respectively.

Specific Experimental Protocols

Experiment 1: the effect of rNTS NTX on PVN NPY-induced feeding. Rats were implanted with 2 cannulas: one into the PVN and one into the rNTS. The treatments are listed in Table 1. Order of treatments was counterbalanced, such that each treatment was given to a subset of rats on each day. Each rat received each treatment once with at least 48 h between each session. Food intake was measured at 1, 2, and 4 h postinjection.

                              
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  		Table 1.   Treatment groups for experiment 1 

Experiment 2: the effect of rNTS NTX on PVN NPY-induced alterations in feeding and BAT UCP and LPL gene expression. Injections were given every 6 h for 24 h. The treatments are listed in Table 2. Food intake and brown fat UCP, LPL, and beta -actin message levels were measured. This experiment was carried out over 2 days (with each experimental group equally represented on both days), and the data were later combined after determining that there was no effect of day (by ANOVA) on feeding response in the control groups.

                              
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  		Table 2.   Treatment groups for experiment 2 

Statistical Analysis

Experiment 1. Data were analyzed by a two-factor repeated-measures ANOVA (NTX × NPY) followed by multiple-comparison contrasts to compare means. Data are expressed as means ± SE.

Experiment 2. Data were analyzed by a one-factor ANOVA followed by the least-significant difference t-test to compare means. Data are expressed as means ± SE. Data were also analyzed by ANOVA to determine whether there was an effect of day on food intake (dependent variable = day, saline groups only). No effect of day on feeding response was found (F1,6 = 0.874, P = 0.3860). The data from animals with misplaced cannulas (n = 7) were analyzed by ANOVA to determine whether an effect on feeding was observed in these animals compared with those with correctly placed cannulas. We then performed power calculations with an effect size of 3.4 g, the largest mean difference between the groups. Data are expressed as means ± SE.

    RESULTS
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Abstract
Introduction
Methods
Results
Discussion
References

Experiment 1

In this experiment, food intake was measured after NPY injection into the PVN, along with saline or 5, 10, or 25 µg NTX in the rNTS. Table 3 shows the periodic feeding response in all treatment groups. In the 0-1 h time period, there was a main effect of NPY (F1,104 = 98.987, P = 0.0001) and of NTX (F3,104 = 5.770, P = 0.0011) on feeding, with no interaction between NPY and NTX (F3,104 = 1.517, P = 0.2146, Table 3). In the 1-2 h and 2-4 h time periods, there was a main effect of NPY (F1,104 = 46.457, P = 0.0001 and F1,104 = 24.784, P = 0.0001, respectively) but no main effect of NTX alone on feeding (Table 3). NPY significantly increased food intake above control levels. NTX alone (5, 10, and 25 µg) in the rNTS did not decrease baseline feeding. The feeding response to PVN NPY was significantly and dose dependently decreased by 10 and 25 µg NTX in the rNTS within the first hour (Table 3). Cumulative feeding responses are shown in Fig. 2. The 10- and 25-µg doses of rNTS NTX were effective in reducing PVN NPY-induced 0-4 h food intake. Although there were four animals with incorrectly placed cannulas, only one rat had a misplaced NTS cannula exclusively (2 had misplaced PVN cannulas and one had both NTS and PVN cannulas misplaced). Injection of NTX into the rNTS in this rat failed to decrease NPY-induced feeding.

                              
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  		Table 3.   Periodic feeding response to 0, 5, 10, and 25 µg NTX injected in the rNTS and 0 or 1 µg NPY injected in the PVN


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  		Fig. 2.   Effect of rNTS naltrexone (NTX; 0, 5, 10, and 25 µg) on PVN neuropeptide Y (NPY; 0 or 1 µg)-induced food intake (expt 1). Values represent 0-4 h food intake and are expressed as means ± SE; n = 14 rats per group. Values represented by columns not sharing common superscripts are significantly different (P < 0.01).

Experiment 2

In this experiment, rats were injected with NTX (0, 5, 10, or 25 µg) into the rNTS and with NPY (0 or 1 µg) into the PVN every 6 h for 24 h. The last set of injections was at 0800, and the rats were killed at 0900. As shown in Fig. 3, NPY in the PVN resulted in significantly increased feeding at all time points (P < 0.05). The food intake of the NTX + NPY-treated animals was significantly lower with all doses of NTX (P < 0.05) than that of the NPY-treated animals and was not significantly different from the controls. This effect was dose related for short-term (<= 6 h) feeding effects but not after repeated injections. PVN NPY resulted in a significant lowering of BAT UCP mRNA levels (P = 0.0219) and BAT LPL mRNA levels (P = 0.0149). None of the doses of NTX tested in the rNTS (5, 10, and 25 µg) significantly altered PVN NPY effects on UCP mRNA levels (Fig. 4) or LPL mRNA levels (Fig. 5).


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  		Fig. 3.   Effect of rNTS NTX (0, 5, 10, and 25 µg, every 6 h for 24 h) on PVN NPY (1 µg every 6 h for 24 h)-induced food intake (expt 2). * P < 0.01 compared with control (saline) group. ** P < 0.01 compared with zero group (NPY only). Data are expressed as means ± SE; n = 7-9 rats per group.


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  		Fig. 4.   Effect of rNTS NTX (0, 5, 10, and 25 µg, every 6 h for 24 h) on PVN NPY (1 µg every 6 h for 24 h)-induced decrease in brown fat uncoupling protein (UCP) gene expression (expt 2). Data are expressed as means ± SE; n = 7-9 rats per group. OD, optical density. Values represented by columns not sharing common superscripts are significantly different (P < 0.05).


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  		Fig. 5.   Effect of rNTS NTX (0, 5, 10, and 25 µg, every 6 h for 24 h) on PVN NPY (1 µg every 6 h for 24 h)-induced decrease in BAT lipoprotein lipase (LPL) gene expression (expt 2). Data are expressed as means ± SE; n = 7-9 rats per group. Values represented by columns not sharing common superscripts are significantly different (P < 0.05).

Data from animals with misplaced NTS cannulas (n = 7) were compared with data from animals with correctly placed cannulas and analyzed by ANOVA to determine whether NTX administered in regions nearby the NTS would decrease PVN NPY-induced feeding. At no dose was there an effect of NTX administration into regions nearby the NTS on PVN NPY-induced feeding (F3,10 = 0.902, P = 0.4738). However, power was calculated at 53%, suggesting that with the addition of more subjects (with misplaced cannulas) a significant result could occur.

    DISCUSSION
Top
Abstract
Introduction
Methods
Results
Discussion
References

In the present study, we further characterized a PVN-to-NTS neural pathway that influences energy metabolism. This pathway is hypothesized to include NPY receptor-containing nerve terminals in the hypothalamic PVN that project to and interact with opioid-releasing nerve terminals within the rNTS in the hindbrain. NPY administered in the PVN results in a robust feeding response (5, 26, 33) and a decrease in UCP gene expression in brown fat (5). On the basis of the previously characterized PVN-NTS neural connection, lesions of which alter feeding behavior (14, 15), and our observation that NTX administered in the rNTS blocked feeding and energy expenditure effects of NPY administered in PVN (18), we proposed that opioid receptors within the rNTS are stimulated after NPY administration in the PVN. However, in our previous studies we administered 50 µg NTX in the rNTS, a relatively large dose with potential for receptor generalization effects such that responses observed with this dose may or may not have been due to opioid receptor blockade. Thus the present study was undertaken to determine the lowest effective dose of NTX in the rNTS on feeding and energy expenditure effects of NPY administered in the PVN.

The short-term effect of NTX in the rNTS on feeding produced by NPY in the PVN was significant and dose responsive (Table 3). The 10- and 25-µg doses of NTX significantly reduced 0-1 h feeding response induced by NPY administration in the PVN, whereas NTX alone in the rNTS did not decrease baseline feeding at any dose (Table 3, Fig. 2). The lowest effective dose of NTX was 10 µg during the 0-1 h time period. The effect of repeated injections of all doses of NTX on feeding produced by NPY administration in the PVN was significant but not dose responsive (Fig. 3). All doses of NTX (5, 10, and 25 µg) significantly reduced the 0-26 h feeding response. Although the 0-26 h feeding reduction by NTX was not dose related, the pattern of feeding reduction observed in the first hour after injection was dose responsive and similar to that observed in the first study. It is possible that with repeated doses a floor effect occurs such that further stimulation of opioid receptors by antagonist fails to produce inhibition of PVN NPY-induced feeding. It is also possible that NPY interacts with additional nonopioid pathways in stimulating feeding.

In previous studies in our laboratory, we have found that NPY administration into the PVN results in decreased UCP message levels (5), an effect that is independent of food intake (4). We have also reported decreases in brown fat UCP gene expression following endogenous increases in NPY gene expression and peptide levels induced by carbohydrate feeding (12). The present data are in accord with this inverse relationship between NPY and brown fat activity. However, whereas feeding produced by PVN NPY administration was significantly and dose dependently decreased by NTX in the rNTS, none of the doses of NTX significantly altered the response of UCP gene expression to NPY stimulation. All rats in the NPY-treated groups had decreased levels of UCP mRNA, and NTX did not block this effect (Fig. 4). PVN NPY administration also significantly decreased BAT LPL gene expression, and rNTS NTX administration did not significantly inhibit this response (Fig. 5). Previously, we reported that a higher dose of NTX (50 µg) in the rNTS reversed PVN NPY effects on BAT UCP mRNA. It appears that the feeding-inhibitory effect of NTX on PVN NPY-induced feeding requires lower doses than that required for inhibition of NPY-induced suppression of BAT activity.

To further confirm neuroanatomical specificity of the rNTS NTX effect on PVN NPY-induced feeding, we analyzed the data from rats with cannulas incorrectly placed within the NTS. NTX injection into animals with incorrectly placed NTS cannulas had no effect on PVN NPY-induced feeding, indicating that the effects observed are due to blockade of opioid receptors in the NTS and not at a site to which the NTX may have diffused. However, due to the moderate power in this analysis, it is possible that the inclusion of more animals with misplaced cannulas would influence the results of the statistical analysis of these data. Additionally, the 1-µl volume used for the injections may be large enough to allow for diffusion into sites near to the NTS.

The feeding produced by NPY in the PVN was not completely blocked by rNTS NTX as we previously observed with a higher dose of NTX (50 µg) injected repeatedly (18). It is possible that because the cannula placement within the rNTS was unilateral, opioid receptors in the contralateral rNTS were still functioning at an uninhibited level. The 50-µg dose used in the previous study may have been sufficient to allow for some NTX to diffuse to the contralateral side, whereas the largest dose (25 µg) in this study was not.

The dose-related nature of the feeding response and the low dose requirement within the first hour after rNTS NTX plus PVN NPY injection supports rNTS involvement in PVN NPY effects on feeding. The lack of effect of rNTS NTX on PVN NPY-induced suppression of BAT activity in this study sheds doubt on the role of the rNTS in PVN NPY effects on BAT and reveals a possible divergence in the PVN NPY feeding-stimulatory and brown fat-inhibitory pathway, such that the feeding-stimulatory effects of NPY in the PVN may be routed through the rNTS whereas PVN NPY effects on brown fat may result from alterations at a different neural site.

Perspectives

The present studies further characterize an energy-signaling neural pathway from the hypothalamic PVN to the hindbrain NTS and illustrate ways that different brain sites might interact to regulate food intake behavior and energy metabolism. The PVN is a center coordinating energy homeostasis, and the NTS is a gustatory relay center with connections to major hypothalamic structures. NPY in the PVN induces feeding and decreases energy expenditure by decreasing the sympathetic outflow to brown adipose tissue. Both the feeding-stimulatory and brown fat-inhibitory effects of NPY in the PVN are blocked by high doses of opioid antagonist administered into the rNTS. However, at lower doses of opioid antagonist, the feeding, but not the brown fat-inhibitory, effects of NPY in the PVN are blocked. These findings indicate that feeding signals originating on stimulation of NPY receptors in the PVN are routed through opioid pathways in the rNTS, whereas signals conveying energy expenditure information may be directed through opioid receptors present in neural centers nearby or within other regions of the NTS. Future studies focusing on dissection of neural pathways controlling energy intake and energy expenditure will provide an important knowledge base from which to draw when considering therapeutic approaches for the treatment of obesity and other energy-related disorders.

    ACKNOWLEDGEMENTS

The technical assistance provided by Dr. James Pomonis is greatly appreciated.

    FOOTNOTES

This work was supported by the Department of Veterans Affairs, National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-42698, and the National Institute on Drug Abuse Grant DA-03999.

Address for reprint requests: C. Kotz, Veterans Affairs Medical Center, One Veterans Drive, Research Route 151, Minneapolis, MN 55417.

Received 30 July 1997; accepted in final form 23 April 1998.

    REFERENCES
Top
Abstract
Introduction
Methods
Results
Discussion
References

1.   Akil, H., S. J. Watson, E. Young, M. E. Lewis, H. Khachaturian, and M. E. Walker. Endogenous opioids: biology and function. Annu. Rev. Neurosci. 7: 223-255, 1984[Medline].

2.   Allen, J. M., and J. I. Koenig. Central and Peripheral Significance of Neuropeptide Y and Its Related Peptides. New York: The New York Academy of Sciences, 1990.

3.   Barraco, I. R. A. Nucleus of the Solitary Tract. Boca Raton, FL: CRC, 1994.

4.   Billington, C. J., J. E. Briggs, M. Grace, and A. S. Levine. Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am. J. Physiol. 260 (Regulatory Integrative Comp. Physiol. 29): R321-R327, 1991[Abstract/Free Full Text].

5.   Billington, C. J., J. E. Briggs, S. Harker, M. Grace, and A. S. Levine. Neuropeptide Y in hypothalamic paraventricular nucleus: a center coordinating energy metabolism. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R1765-R1770, 1994[Abstract/Free Full Text].

6.   Chang, C. L., Y. C. Tsai, S. S. Lin, and J. T. Cheng. Effect of premedication on the changes of neuropeptide Y (NPY) in anesthesia. Ma Tsui Hsueh Tsa Chi 30: 147-152, 1992.

7.   Chomczynski, P., and N. Sacchi. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162: 156-159, 1987[Medline].

8.   Clark, J. T., P. S. Kalra, W. R. Crowley, and S. P. Kalra. Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology 115: 427-429, 1984[Abstract].

9.   Contreras, R. J., T. Kosten, and E. Bird. Area postrema: part of the autonomic circuitry of caloric homeostasis. Federation Proc. 43: 2966-2968, 1984[Medline].

10.   Edwards, G. L., and R. C. Ritter. Ablation of the area postrema causes exaggerated consumption of preferred foods in the rat. Brain Res. 216: 265-276, 1981[Medline].

11.   Giraudo, S. Q., C. J. Billington, and A. S. Levine. Effect of the opioid antagonist naltrexone on feeding induced by DAMGO in the central nucleus of the amygdala and in the paraventricular nucleus in the rat. Brain Res. 782: 18-23, 1998[Medline].

12.   Giraudo, S. Q., C. M. Kotz, M. K. Grace, C. J. Billington, and A. S. Levine. Differences in rat hypothalamic NPY mRNA and brown fat uncoupling protein mRNA after one week of high-carbohydrate or high-fat diets. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R1578-R1583, 1994[Abstract/Free Full Text].

13.   Gosnell, B. A., and A. S. Levine. Stimulation of Ingestive Behavior by Preferential and Selective Opioid Agonists. New York: Academic, 1996.

14.   Kirchgessner, A. L., and A. Sclafani. PVN-hindbrain pathway involved in the hypothalamic hyperphagia-obesity syndrome. Physiol. Behav. 42: 517-528, 1988[Medline].

15.   Kirchgessner, A. L., A. Sclafani, and G. Nilaver. Histochemical identification of a PVN-hindbrain feeding pathway. Physiol. Behav. 42: 529-543, 1988[Medline].

16.   Kotz, C. M., C. J. Billington, and A. S. Levine. Opioids in the nucleus of the solitary tract are involved in feeding in the rat. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol. 41): R1028-R1032, 1997[Abstract/Free Full Text].

17.   Kotz, C. M., M. K. Grace, C. J. Billington, and A. S. Levine. The effect of norbinaltorphimine, beta -funaltrexamine, and naltrindole on NPY-induced feeding. Brain Res. 631: 325-328, 1993[Medline].

18.   Kotz, C. M., M. K. Grace, J. Briggs, A. S. Levine, and C. J. Billington. Effects of opioid antagonists naloxone and naltrexone on neuropeptide Y-induced feeding and brown fat thermogenesis in the rat: neural site of action. J. Clin. Invest. 96: 163-170, 1995.

19.   Kotz, C. M., M. K. Grace, J. E. Briggs, C. J. Billington, and A. S. Levine. Naltrexone induces arcuate nucleus neuropeptide Y gene expression in the rat. Am. J. Physiol. 271 (Regulatory Integrative Comp. Physiol. 40): R289-R294, 1996[Abstract/Free Full Text].

20.   Lambert, P. D., J. D. Wilding, A. A. al-Dokhayel, S. G. Gilbey, and S. R. Bloom. The effect of central blockade of kappa-opioid receptors on neuropeptide Y-induced feeding in the rat. Brain Res. 629: 146-148, 1993[Medline].

21.   Lambert, P. D., J. P. H. Wilding, A. A. M. al-Dokhayel, C. Bohuon, E. Comoy, S. G. Gilbey, and S. R. Bloom. A role for neuropeptide-Y, dynorphin, and noradrenaline in the central control of food intake after food deprivation. Endocrinology 133: 29-32, 1993[Abstract].

22.   Lambert, P. D., J. P. H. Wilding, A. A. M. al-Dokhayel, S. G. Gilbey, M. A. Ghatei, and S. R. Bloom. Naloxone-induced anorexia increases neuropetide Y concentrations in the dorsomedial hypothalamus: evidence for neuropeptide Y interactions in the control of food intake. Peptides 15: 657-660, 1994[Medline].

23.   Levine, A. S., M. Grace, and C. J. Billington. The effect of centrally administered naloxone on deprivation and drug-induced feeding. Pharmacol. Biochem. Behav. 36: 409-412, 1990[Medline].

24.   Levine, A. S., and J. E. Morley. Neuropeptide Y: a potent inducer of consummatory behavior in rats. Peptides 5: 1025-1029, 1984[Medline].

25.   Mansour, A., C. A. Fox, S. Burke, F. Meng, R. C. Thompson, H. Akil, and S. J. Watson. Mu, delta and kappa opioid receptor mRNA expression in the rat CNS: an in situ hybridization study. J. Comp. Neurol. 350: 412-438, 1994[Medline].

26.   Morley, J. E., A. S. Levine, B. A. Gosnell, J. Kneip, and M. Grace. Effect of neuropeptide Y on ingestive behaviors in the rat. Am. J. Physiol. 252 (Regulatory Integrative Comp. Physiol. 21): R599-R609, 1987[Abstract/Free Full Text].

27.   Pages, N., M. Orosco, C. Fournier, C. Rouch, A. Hafi, A. Gourch, E. Comoy, and C. Bohoun. The effects of chronic administration of morphine on the levels of brain and adrenal catecholamines and neuropeptide Y in rats. Gen. Pharmacol. 22: 943-947, 1991[Medline].

28.   Paxinos, G., and C. Watson. The Rat Brain in Stereotaxic Coordinates. New York: Academic, 1990.

29.   Sahu, A., W. R. Crowley, and S. P. Kalra. An opioid-neuropeptide-Y transmission line to luteinizing hormone (LH)-releasing hormone neurons: a role in the induction of LH surge. Endocrinology 126: 876-883, 1990[Abstract].

30.   Schick, R. R., V. Schusdziarra, C. Nussbaumer, and M. Classen. Neuropeptide Y and food intake in fasted rats: effect of naloxone and site of action. Brain Res. 552: 232-239, 1991[Medline].

31.   South, E. H., and R. C. Ritter. Over-consumption of preferred foods following capsaicin pretreatment of the area postrema and adjacent nucleus of the solitary tract. Brain Res. 288: 243-251, 1983[Medline].

32.   Stanley, B. G., S. E. Kyrkouli, S. Lampert, and S. F. Leibowitz. Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 7: 1189-1192, 1986[Medline].

33.   Stanley, B. G., and S. F. Leibowitz. Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. Proc. Natl. Acad. Sci. USA 82: 3940-3943, 1985[Abstract/Free Full Text].

34.   Stanley, B. G., W. Magdalin, A. Seirafi, W. J. Thomas, and S. F. Leibowitz. The perifornical area: the major focus of (a) patchily distributed hypothalamic neuropeptide Y-sensitive feeding system(s). Brain Res. 604: 304-317, 1993[Medline].

35.   Thurston, S. J., and J. D. Saffer. Ultraviolet shadowing nucleic acids on nylon membranes. Anal. Biochem. 178: 41-42, 1989[Medline].

Am J Physiol Regul Integr Compar Physiol 275(2):R471-R477
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