| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Group in Endocrinology, Departments of 3 Integrative Biology and 2 Psychology, University of California, Berkeley, California 94720
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Siberian hamsters undergo torpor during the short days of winter and in response to glucoprivation or food restriction. We tested whether the area postrema and the adjacent nucleus of the solitary tract (hereafter the AP), which monitor metabolic fuel availability, also control the onset of torpor. Siberian hamsters that had manifested torpor spontaneously or had entered torpor in response to 2-deoxy-D-glucose (2-DG) treatment were subjected to area postrema ablations (APx). Hamsters continued to display torpor postoperatively; most features of torpor were unaffected by APx. The AP is not necessary for expression of torpor elicited by short day lengths or metabolic challenge. In contrast, decreases in food intake manifested by hamsters treated with 2-DG were counteracted by APx. In Siberian hamsters, the AP appears to mediate effects of 2-DG on food intake but not torpor.
food intake; 2-deoxy-D-glucose
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
DAILY TORPOR
HELPS small mammals cope with limited food availability and low
ambient temperatures. Siberian hamsters decrease their body temperature
(Tb) from euthermic values of 37°C to as low as 15°C
for up to 8 h during torpor (15), thereby
substantially reducing daytime food requirements and subsequently the
amount of nighttime foraging (16) in air temperatures as
low as 
40°C (43).
The physiological triggers of torpor are not known but may to be related to energy availability. Hamsters begin to display torpor after ~10 wk in simulated winter conditions of short day lengths and low temperatures; torpor is preceded by a reduction in food intake, body weight, and white adipose tissue mass, an increase in thermogenic capacity in brown adipose tissue, and concurrent molt to winter pelage (14). The winter phenotype is under photoperiodic control and is transduced by seasonal changes in melatonin secretion (42). Hamsters in the wild rarely experience the confluence of abundant food with exposure to low ambient temperatures and short days (43). Because Siberian hamsters forage throughout the winter months (44) when food quality and quantity are diminished and foraging costs increased, energy savings that accrue from torpor likely contribute importantly to over-winter survival. Torpor occurs spontaneously in anticipation of seasonal energetic shortages in short photoperiod and is also elicited by limited food availability at any time of year (33, 40). In either instance, initiation of torpor is related to mechanisms that monitor existing or predictable energy shortages.
Administration of a glucose utilization inhibitor, 2-deoxy-D-glucose (2-DG), but not a fatty acid utilization inhibitor, mercaptoacetate (MA), reliably induces torpor in Siberian hamsters (7). This form of torpor resembles that which occurs spontaneously in short day lengths or after food restriction. 2-DG induces torpor in a dose-dependent manner, and its effectiveness is potentiated by food restriction (7). Reduced plasma glucose concentrations are correlated with the onset of torpor in Siberian hamsters (6).
The area postrema (AP), a fenestrated circumventricular organ that lies outside the blood-brain barrier, receives terminal afferent input from the vagus nerve and projects to the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus, the lateral parabrachial nucleus, and the hypothalamic paraventricular nucleus (PVN), all of which are major relay nuclei for ascending visceral afferent input to the forebrain in rats (12). Infusion of 2-DG as well as 5-thioglucose (another inhibitor of glucose utilization) into the fourth ventricle but not other brain areas increases short-term food intake (FI) in rats (18, 23). 2-DG (administered intraperitoneally) not alone but in combination with methyl palmoxirate (an inhibitor of fatty acid oxidation administered by gavage) suppresses estrous behavior in Syrian hamsters ovariectomized and treated with estradiol benzoate and progesterone (9). Firing rates of AP neurons are responsive to fluctuations in blood concentrations of glucose (13) and express c-fos in response to food intake in rats (21) and injections of 2-DG and MA in rats (24) and 2-DG in Syrian hamsters (34). Ablation of the AP prevents increases in food intake of rats challenged with 2-DG (5, 11, 25), counteracts the inhibition of estrous cycles in Syrian hamsters treated with a high dose of 2-DG (1,750 mg/kg; Ref. 36), and diminishes the disruption of lordosis in food-restricted Syrian hamsters ovariectomized and treated with estradiol benzoate and progesterone (19) and those injected with 2-DG (36). Collectively, these findings implicate the AP as a major component of the neural system that monitors glucose availability and thereby controls energy-dependent behaviors such as food consumption and estrus. The disruptive effect of 2-DG on estrous behavior could also reflect separate actions of the drug on secretion of gonadal hormones.
The neural pathways that mediate torpor in Siberian hamsters remain to be fully identified. The suprachiasmatic nucleus is necessary for the temporal organization of torpor bouts but not for their expression (29), the pineal is necessary for onset of spontaneous torpor in short day lengths but not that induced by food restriction (41, 42), and the PVN is necessary for spontaneous torpor in a majority of hamsters; its role in torpor elicited by food restriction is unknown (28).
Because torpor is an acutely energy-sensitive process, glucosensitive neurons of the AP (2) are well situated to participate in the control of this behavior. The integrity of the AP may determine whether hamsters can perceive or respond to the changes in metabolic fuels that trigger torpor onset. Individual hamsters adopt one of several tactics when energy demands are high; some utilize torpor bouts liberally, eat less, and reduce nocturnal locomotor activity, whereas others forego hypothermia and instead consume more food and increase nocturnal activity (31). To evaluate the role of the AP in regulation of torpor and food intake, we ablated this structure (APx) in Siberian hamsters that were manifesting spontaneous bouts of torpor; other APx hamsters were challenged with 2-DG treatments that elicit torpor in neurologically intact animals. We anticipated that in the absence of the AP, Siberian hamsters would be less able to assess metabolic fuel availability and consequently less prone to display torpor when challenged with reduced fuel availability.
| |
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Telemetric Recording of Tb
Calibrated temperature-sensitive radiotransmitters (model VM-FH, MiniMitter, Sunriver, OR) for telemetric recording of Tb were implanted intra-abdominally into hamsters under anesthesia induced by a cocktail (50 mg/kg ketamine, 5 mg/kg xylazine, 0.5 mg/kg body wt acepromazine; administered intraperitoneally). A single midline incision was made in the peritoneal cavity, the transmitter was inserted, and the wound was closed with sutures. An analgesic solution (60 mg acetaminophen and 6 mg codeine phosphate/100 ml) was provided in the drinking water for the first 3 days after surgery. Radiofrequency signals from the implanted transmitters were collected every 10 min via receiver boards placed under individual cages. Frequency transmissions were processed by computer (Dataquest Data Acquisition System, St. Paul, MN) and transformed into Tb values.Definition of Torpor
Torpor was considered to occur when Tb was <31°C for a minimum of 30 min. Depth of torpor refers to the absolute minimum temperature (Tb min) reached during a bout of torpor and duration of torpor to the number of minutes Tb was <31°C. Latency to display torpor references the interval from the time of injection of 2-DG to the initial decrease in Tb to <31°C.Surgery
APx designates ablation of the AP plus adjacent NTS unless otherwise noted. APx was performed under anesthesia as described above. Hamsters were placed in a stereotaxic instrument, and an incision was made from the occipital crest to the midcervical level. The top muscle layer was removed to expose the occipital bone. The foramen magnum was enlarged, the dura was removed, and the cerebellum was lifted to visualize the AP, which was removed by suction with an aspiration needle. Bleeding was controlled by inserting absorbable foam (Gel Foam, Upjohn, Kalamazoo, MI) into the foramen magnum when necessary. The muscles were then sutured and treated with 0.1% nitrofurazone ointment. Sham-operated animals underwent the same treatment except the AP was not removed. Postoperatively, acetaminophen and codeine were added to the drinking water for 3 days.Histological Assessment
Hamsters were deeply anesthetized with pentobarbital sodium (80 mg/kg body wt) and perfused transcardially with a mixture of 15 ml of 0.9% NaCl and 0.75 ml Evans blue (100 mg/ml; Sigma Chemical, St. Louis, MO; dissolved in NaCl at pH 7.4), followed by buffered Formalin. Brains were postfixed for at least 2 h in Formalin and embedded in paraffin; frozen sections were cut at 15 µm throughout the AP region, stained with cresyl violet, and mounted onto slides for histological verification of extent of brain lesions.Statistics
The Statview statistics package (Abacus Concepts, Berkeley, CA) was used for all statistical analyses. Mean differences between groups were analyzed by ANOVA with repeated measures where appropriate. Where significant F ratios were obtained for one-way ANOVA, group means were compared with Fisher's protected least significance difference test (Fisher's PLSD). Comparisons involving frequencies were made using
2 or Fisher's exact test. Correlations
between variables were evaluated with the squared Pearson correlation
coefficient. Results were considered significant if P < 0.05 with two-tailed tests and are reported as such regardless of
actual P value. Number of animals represents individuals per
group with working transmitters on the day of treatment, not total
number of animals treated. Values are reported as means ± SE.
Experiment 1: Role of AP in Torpor Induced by 2-DG
Animals. Adult male hamsters (Phodopus sungorus), maintained from birth in a 16:8-h light-dark photoperiod (lights on 0300, Pacific standard time) at 23 ± 2°C, were fed Purina Rodent Chow 5015 and water ad libitum. Eight weeks before APx or sham surgery, animals were transferred to a cold room (15°C) with an identical photoperiod and individually housed in polypropylene cages (25 × 14 × 12 cm) with wood shavings for bedding and cotton nesting material. Two weeks later, radiotransmitters were implanted intra-abdominally into hamsters whose body weights were recorded weekly thereafter. Animals that underwent either APx (n = 24) or sham surgery (n = 18) were allowed to recover at an ambient temperature of 23°C for 1-2 days postoperatively and were then returned to 15°C. 2-DG (Sigma; doses of 2,250 and 2,500 mg/kg, 625 mg/ml ddH2O ip) and saline were administered to each hamster in a counterbalanced design with 1 wk between injections, beginning 3-5 wk after surgery. All injections were given between 0800 and 0900. No pretest was administered, because 2-DG doses in the range that were used in the present study were previously demonstrated to reliably induce torpor in ~50-80% of hamsters tested (6, 39), and propensity for torpor in one test was not highly predictive of another bout within individual hamsters.
FI measurements. After hamsters were acclimated for 7 days to the disturbance involved with measuring FI, 24-h food consumption was recorded daily, beginning 2 days before and ending 2 days after drug treatment. Food was stored in the cold room 1 wk before being dispensed to hamsters to compensate for changes in weight due to moisture absorption in the cold.
Experiment 2: Role of the AP in Spontaneous Torpor
Animals. A second cohort of adult male Siberian hamsters was transferred from the 16:8-h light-dark photocycle to a short photoperiod (8:16-h light-dark cycle, lights on at 0830) and low temperature (15°C) at 3-4 mo of age; 12 wk later they were monitored for a suite of winter responses including gonadal regression (assessed by palpation), decreased body weights (>10%), and onset of molt to a winter coat (pelage score >2) (10). Transmitters were implanted in animals that demonstrated these winter responses; those that manifested at least two torpor bouts over the next 4 wk were designated for APx or sham operations. Sixteen APx and six sham hamsters were monitored for 14-17 wk postoperatively.
FI measurements. Twenty-four-hour food consumption was recorded every day between 1400 and 1600 for 6 wk postoperatively.
Activity monitoring. Gross locomotor activity was measured using the same biotelemetry system as for Tb recordings. Activity data were recorded as the total number of locomotor movements that occurred in a 10-min interval. A minimum distance of 30 cm between adjacent boards was maintained to minimize interference between transmitters. Activity data were collected for 2 wk beginning 2 mo after neural surgery.
All procedures were approved by the University of California at Berkeley Animal Care and Use Committee.| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Lesion Verification
The AP was completely ablated in 18 and 14 hamsters in experiments 1 and 2, respectively. Damage to the NTS varied between 0-25% and 75-100%. The hypoglossal nucleus also sustained minimal damage (<25%). Damage to the NTS and hypoglossal nucleus was determined at or near the level of the AP. As such, some residual NTS is likely to be present further rostrally and caudally. Representative photomicrographs are shown in Fig. 1. Extent of damage to the NTS or hypoglossal nucleus did not affect the propensity for animals to undergo torpor. For purposes of data analysis, animals were consequently assigned to either APx or sham groups. Visible damage to the AP was undetectable in all Sham hamsters.
|
Experiment 1
APx and 2-DG-induced torpor.
Hamsters with complete ablation of the AP continued to manifest torpor
when treated with 2,500 mg/kg 2-DG (Table
1). At the lower dose (2,250 mg/kg), only the sham animals responded with a torpor bout, but the
sham and APx groups did not differ significantly (2 = 3.29; P > 0.05). As expected, no hamster entered
torpor when injected with the saline vehicle. Neither the percentage of
torpid animals (2 = 0.95; P > 0.05), the duration of torpor
[F(1,11) = 2.3;
P > 0.05], nor the latency to undergo torpor
[F(1,11) = 0.34;
P > 0.05] differed between APx and sham animals
treated with the higher dose of 2-DG (Table 1).
|
Effects of surgery on body weight.
There was a significant effect of time and an interaction of time with
lesion but not of lesion alone [time:
F(1,12) = 16.2, P < 0.05; interaction:
F(1,12) = 4.9, P < 0.05; lesion F(1,1) = 4.0, P > 0.05]. Body weights did not differ
preoperatively between APx and sham hamsters (t-test;
P > 0.05). Postoperatively, the body weights of APx
hamsters were depressed compared with preoperative values until the
time of the first treatment (2,250 and 2,500 mg/kg 2-DG or vehicle
injection; t-test; P < 0.05) but did not differ significantly from those of sham animals at the time of the
second and third treatments (t-test; P > 0.05; Fig 2).
|
APx and FI.
Both doses of 2-DG decreased FI of sham hamsters (Fig.
3); on the day of and the day after 2-DG
injection (days 0 and 1), FI was depressed to
<50% of pretreatment values (day 1) (t-test; P < 0.05). Recovery to baseline FI values was complete
on day 2. This relation held regardless of whether or not
2-DG induced torpor. In contrast, 2-DG treatment was completely
ineffective in suppressing FI in APx hamsters on either the day of
treatment or the subsequent day (t-test; P > 0.05). APx and sham hamsters injected with saline did not change their
FI (t-test; P > 0.05; Fig. 3).
|
Experiment 2
APx and torpor induced by short days.
All hamsters manifested torpor preoperatively; APx and sham groups had
comparable numbers of such bouts over 4 wk [3 ± 0.6 and 4 ± 0.8; F(1,16) = 1.1, P > 0.05]. Postoperatively, all animals continued to
undergo torpor; the mean number of such bouts displayed over the course
of 14-17 wk was comparable for both groups
[F(1,16) = 1.1, P > 0.05; Table 2].
|
Circadian timing of torpor. Circadian distribution of torpor bouts did not differ between sham and APx hamsters. Torpor was initiated a few hours before or during the light phase, except for one APx animal that initiated four bouts at the onset of the dark phase (1 pre- and 3 postoperatively). Except for one APx hamster, no animal displayed more than one torpor bout per day.
There was a positive correlation (r2 = 0.55; P < 0.05) between the length of the torpor season (beginning of torpor onset preoperatively to last torpor bout postoperatively) and total number of bouts, but there was no relation between onset of torpor season and total number of torpor bouts (r2 = 0.02; P > 0.05) for both groups of animals. Mean activity counts for individual hamsters during the first 4 h after a torpor bout were reduced compared with the number of counts for the same interval on normothermic days (16.4 ± 2.4 vs. 32.0 ± 4.4; t-test; P < 0.05). Food consumption decreased as the number of torpor bouts increased (r2 = 0.41; P < 0.05).FI. APx hamsters consumed slightly less food (4.0 g) on the day of spontaneous torpor (day 0) than during the preceding 24 h (4.6 g; t-test; P < 0.05) and recovered to baseline values the day after torpor. FI of sham hamsters did not differ significantly on the day of torpor from values the day before or the day after torpor (t-test; P > 0.05).
Effects of surgery on body weight. There was a significant effect of time and an interaction of time with lesion but not of lesion alone [time: F(1,15) = 6.1, P < 0.05; interaction: F(1,15) = 2.7, P < 0.05; lesion: F(1,1) = 0.034, P > 0.05]. Body weight did not differ significantly between groups at any point during the experiment.
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Even though the AP is involved in monitoring energy availability and energy availability influences torpor, ablations of the AP did not prevent the occurrence of torpor in response to treatment with high doses of 2-DG or prolonged exposure to winter day lengths in Siberian hamsters. Torpor survived APx with little change from preoperative baseline values in frequency, duration, and depth of bouts. APx appeared marginally effective in decreasing the incidence of torpor in hamsters treated with a lower dose of 2-DG; perhaps the AP mediates metabolic challenges that more closely simulate those within the physiological range. The monitoring of energy availability by AP neurons is not necessary for expression of torpor in short day lengths; structures distinct from the AP are sufficient to induce the hypometabolic state. These findings do not, however, preclude AP participation in monitoring fuel shortages that induce torpor in neurologically intact hamsters.
The mechanism by which 2-DG triggers torpor expression in Siberian hamsters has been questioned recently. Whereas plasma glucose concentrations decline during entry and increase during arousal from torpor, injections of insulin that produce similar levels of hypoglycemia as occur during spontaneous torpor did not trigger a decline in Tb (6). It remains possible that the extreme glucoprivation produced by 2-DG affects brain sites distinct from those engaged by insulin treatment or exposure to short day lengths.
Contrary to its lack of effect on torpor, APx either eliminated or substantially attenuated changes in food intake induced by 2-DG in hamsters. The counteractive effect of APx on FI was evident regardless of whether 2-DG treatment also induced torpor. High doses of 2-DG may act on the AP to suppress food intake but induce torpor via a different mechanism. It can be argued that the extreme glucoprivation used in this study made the hamsters ill. The AP has been implicated as a chemoreceptor trigger zone for emesis; the vomiting response to most but not all emetic drugs is abolished by APx (reviewed in Ref. 17). It is unknown whether or not 2-DG at any dose induces vomiting in Siberian hamsters. We have not observed any such response with the current doses of 2-DG (2,250 and 2,500 mg/kg) or with lower doses (800 and 1,500 mg/kg; Ref. 7). Interestingly, a 1,000-mg/kg dose of 2-DG administered to neurologically intact deermice (Peromyscus maniculatus) slightly suppressed food intake during the first 3 h after treatment, but the same stimulus elicited hyperphagia in neurologically intact house mice; no general debilitation was noted in either species (27). We cannot, however, completely discount the possibility that the decrease in FI observed in AP-intact hamsters administered 2-DG in the present study were due to nausea (without vomiting) or other ill effects associated with high doses of 2-DG. Similarly, 2-DG may depress food consumption in intact hamsters because the drug produces physiological manifestations of stress. Consequently, elimination of hypophagia in APx hamsters treated with 2-DG may reflect the absence or amelioration of illness or stress after drug treatment, rather than a direct effect on mechanisms that control food intake.
Siberian hamsters decrease, laboratory rats increase, and Syrian hamsters do not change FI in response to 2-DG (22, 37). These apparent species differences may in part reflect differences in methodology rather than interspecific variation; the typical dose of 2-DG administered to rats is usually <400 mg/kg, compared with >1,500 mg/kg in Syrian and Siberian hamsters; also, posttreatment measures of FI were typically short term (<6 h) in rats compared with 24 h for Syrian and Siberian hamsters (20, 22, 39). The response to 2-DG may be dose related; a low dose (125 mg/kg 2-DG) insufficient to increase FI in rats increased FI in Siberian hamsters tested 2-24 h posttreatment (3), whereas higher doses (2,250 and 2,500 mg/kg 2-DG) in the present study decreased FI in neurologically intact Siberian hamsters.
The high doses of 2-DG used in the present study are potentially toxic, at least in some rodent species. The 1,000-, 1,250-, 1,500-, 1,750-, and 2,000-mg/kg doses of 2-DG decrease FI and produce ataxia within seconds that ends several minutes later in some Syrian hamsters (22, 35). The latency between 2-DG injection and torpor was ~40 min for Siberian hamsters, and hypothermia was sustained for 2 h in the present study. Injections of 1,000 mg/kg 2-DG in gerbils resulted in lethargy and depression of FI (26), whereas 500 mg/kg 2-DG (administered iv) produced lethargy in rats (no FI measures were taken) (4). Common features of treatment with high doses of 2-DG in rats, gerbils, and Syrian hamsters include varying degrees of lethargy, stupor, and hypothermia. In contrast, treatment with 2,500 mg/kg 2-DG did not elicit torpor or ataxia in deermice, another photoperiodic species capable of undergoing seasonal torpor (38). In addition, house mice eat more and do not become lethargic when administered 1,000 mg/kg 2-DG (27).
2-DG at 2,500 or 2,000 mg/kg (a lower dose sometimes effective in inducing torpor) elicits a significant and sustained reduction in Tb and subsequent spontaneous recovery to euthermia that resembles naturally occurring seasonal torpor in Siberian hamsters (7). 2-DG has been a convenient tool in studying torpor, because the response is elicited in Siberian hamsters within an hour of injection; spontaneous torpor often is not manifested until Siberian hamsters have been held in short day lengths for up to 16 wk. The use of this drug also has advantages over food deprivation in that hamsters are spared prolonged periods of food restriction that must produce substantial loss of body weight before torpor is displayed. The two forms of torpor (spontaneous and drug induced) yielded comparable results regarding the role of the AP; the nonpharmacological approach is, nevertheless, likely of greater relevance to an understanding of seasonal torpor.
Ablation of the AP had little impact on ad libitum FI of Siberian hamsters that were undergoing seasonal torpor during extended exposure to short day lengths. Short-day adaptations may render further adjustments in feeding unnecessary, whether torpor is utilized or not; the AP may not be involved in the mechanisms that mediate the gradual reductions in FI that precede bouts of spontaneous torpor (32).
The reduction in locomotor activity after spontaneous bouts of torpor was most evident 4 h after torpor onset. The 48% reduction in mean activity recorded in the first 4 h after torpor (corresponding to 3 h before the onset of the dark phase) compares with a 71% reduction reported previously (30). Reduced activity after bouts of spontaneous torpor may represent sleep, a homologous process that, in common with torpor, functions to conserve energy; electroencephalogram slow-wave activity is enhanced in Siberian hamsters after a bout of spontaneous torpor in a manner similar to that found after sleep deprivation (8). Unlike Ruf and Heldmaier (30), however, we did not observe decreased activity over the course of the entire dark phase after a torpor bout. This decrease may represent reduced foraging efforts in the field and reflect reduced energy needs due to savings accrued during torpor. Any of several procedural differences may account for the discrepant findings. Amount of food consumed was negatively correlated with the number of torpor bouts for hamsters at 18 and 23°C (31) and was confirmed in this study for animals kept at 15°C. This suggests that, on a given night for a given individual, different tactics may be used in response to the same challenge; in some instances, hamsters may display torpor, eat little, and move little, whereas others will forego torpor, eat, and move about, presumably in search of food (31).
The role of AP in torpor induced by food restriction was not addressed in the present study; the milder energetic challenges presented by food restriction could be mediated through the AP, but we consider this unlikely. Delays in puberty associated with food restriction were not reversed by ablating the AP in mice (1), and the absence of the AP did not affect the ability of 2-DG to elicit arousal from hibernation in ground squirrels (J. Dark, D. R. Miller, H. H. Bae, and D. A. Lewis, unpublished data), although the suppression of estrous behavior induced by food restriction in Syrian hamsters was reversed by APx (19). Thus many but not all energy-sensitive processes are dependent on the AP.
Collectively, the present results demonstrate that the AP is not necessary for the expression of torpor in male Siberian hamsters but is critical for modifications in FI induced by 2-DG. The AP is not implicated in modulation of FI of Siberian hamsters undergoing spontaneous torpor in winter day lengths. The integrity of the AP is evidently more important for the control of FI than for torpor.
| |
ACKNOWLEDGEMENTS |
|---|
We are grateful to Betty Cho, Dawn Miller, and Christina Tuthill for excellent technical assistance; Thu Dinh at Washington State University for demonstrating the AP surgery; and David Freeman, Jennie Larkin, Brian Prendergast, and two anonymous reviewers for helpful comments on the manuscript.
| |
FOOTNOTES |
|---|
This research was supported by National Institutes of Health Grants NS-30816 and HD-02982.
Address for reprint requests and other correspondence: H. Bae, 2568 Virginia St., Berkeley, CA 94709 (E-mail: hbae{at}socrates.berkeley.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Received 12 February 1999; accepted in final form 20 July 1999.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Acuff, HB,
Olejniczak JA,
Jerrad LE,
and
Anson HI.
The role of the area postrema (AP) in the onset of puberty in the food-restricted, prepubertal female rat (Abstract).
Biol Reprod
56, Suppl1:
159,
1997.
2.
Adachi, A,
Kobashi M,
Miyoshi N,
and
Tsukamoto G.
Chemosensitive neurons in the area postrema of the rat and their possible functions.
Brain Res Bull
26:
137-140,
1991[ISI][Medline].
3.
Bartness, TJ,
Morley JE,
and
Levine AS.
Effects of food deprivation and metabolic fuel utilization on the photoperiodic control of food intake in Siberian hamsters.
Physiol Behav
57:
61-68,
1995[Medline].
4.
Breier, A,
Crane AM,
Kennedy C,
and
Sokoloff L.
The effects of pharmacologic doses of 2-deoxy-D-glucose on local cerebral blood flow in the awake, unrestrained rat.
Brain Res
618:
277-282,
1993[ISI][Medline].
5.
Contreras, RJ,
Fox E,
and
Drugovich ML.
Area postrema lesions produce feeding deficits in the rat: effects of preoperative dieting and 2-deoxy-D-glucose.
Physiol Behav
29:
875-884,
1982[Medline].
6.
Dark, J,
Lewis DA,
and
Zucker I.
Hypoglycemia and torpor in Siberian hamsters.
Am J Physiol Regulatory Integrative Comp Physiol
276:
R776-R781,
1999
7.
Dark, J,
Miller DR,
and
Zucker I.
Reduced glucose availability induces torpor in Siberian hamsters.
Am J Physiol Regulatory Integrative Comp Physiol
267:
R496-R501,
1994
8.
Deboer, T,
and
Tobler I.
Sleep EEG after daily torpor in the Djungarian hamster: similarity to the effects of sleep deprivation.
Neurosci Lett
166:
35-38,
1994[ISI][Medline].
9.
Dickerman, RW,
Li H,
and
Wade GN.
Decreased availability of metabolic fuels suppresses estrous behavior in Syrian hamsters.
Am J Physiol Regulatory Integrative Comp Physiol
264:
R568-R572,
1993
10.
Duncan, MJ,
and
Goldman BD.
Hormonal regulation of the annual pelage color cycle in the Djungarian hamster, Phodopus sungorus.
J Exp Zool
230:
89-95,
1984[ISI][Medline].
11.
Edmonds, BK,
and
Edwards GL.
Dorsomedial hindbrain participation in glucoprivic feeding response to 2DG but not 2DG-induced hyperglycemia or activation of the HPA axis.
Brain Res
801:
21-28,
1998[ISI][Medline].
12.
Ferguson, AV,
and
Lowes VL.
Functional neural connections of the area postrema.
In: Nucleus of the Solitary Tract, edited by Barraco I.. Boca Raton, FL: CRC, 1994, p. 147-157.
13.
Funahashi, M,
and
Adachi A.
Glucose-responsive neurons exist within the area postrema of the rat: in vitro study on the isolated slice preparation.
Brain Res Bull
32:
531-535,
1993[ISI][Medline].
14.
Goldman, BD,
Darrow JM,
Duncan MJ,
and
Yogev L.
Photoperiod, reproductive hormones, and winter torpor in three hamster species.
In: Living in the Cold: Physiological and Biochemical Adaptations, edited by Heller HC,
Musacchia XJ,
and Wang LCH. New York: Elsevier, 1986, p. 341-351.
15.
Heldmaier, G,
and
Steinlechner S.
Seasonal pattern and energetics of short daily torpor in the Djungarian hamster, Phodopus sungorus.
Oecologia (Berl)
48:
265-270,
1981.
16.
Heldmaier, G,
and
Steinlechner S.
Seasonal control of energy requirements for thermoregulation in the Djungarian hamster (Phodopus sungorus), living in natural photoperiod.
J Comp Physiol
142:
429-437,
1981.
17.
Miller, AD,
and
Leslie RA.
The area postrema and vomiting.
Front Neuroendocrinol
15:
301-120,
1994[ISI][Medline].
18.
Murahashi, K,
Bucholtz DC,
Nagatani S,
Tsukahara S,
Tsukamura H,
Foster DL,
and
Maeda K.
Suppression of luteinizing hormone pulses by restriction of glucose availability is mediated by sensors in the brain stem.
Endocrinology
137:
1171-1176,
1996[Abstract].
19.
Panicker, AK,
Mangels RA,
Powers JB,
Wade GN,
and
Schneider JE.
AP lesions block suppression of estrous behavior, but not estrous cyclicity, in food-deprived Syrian hamsters.
Am J Physiol Regulatory Integrative Comp Physiol
275:
R158-R164,
1998
20.
Penicaud, L,
Thompson DA,
and
Le Magnen J.
Effects of 2-deoxy-D-glucose on food and water intake and body temperature in rats.
Physiol Behav
36:
431-435,
1986[Medline].
21.
Rinaman, L,
Baker EA,
Hoffman GE,
Stricker EM,
and
Verbalis JG.
Medullary c-fos activation in rats after ingestion of a satiating meal.
Am J Physiol Regulatory Integrative Comp Physiol
275:
R262-R268,
1998
22.
Ritter, RC,
and
Balch OK.
Feeding in response to insulin but not to 2-deoxy-D-glucose in the hamster.
Am J Physiol Endocrinol Metab Gastrointest Physiol
234:
E20-E24,
1978
23.
Ritter, RC,
Slusser PG,
and
Stone PG.
Glucoreceptors controlling feeding and blood glucose: location in the hindbrain.
Science
213:
451-453,
1981
24.
Ritter, S,
and
Dinh T.
2-Mercaptoacetate and 2-deoxy-D-glucose induce Fos-like immunoreactivity in rat brain.
Brain Res
641:
111-120,
1994[ISI][Medline].
25.
Ritter, S,
and
Taylor JS.
Vagal sensory neurons are required for lipoprivic but not glucoprivic feeding in rats.
Am J Physiol Regulatory Integrative Comp Physiol
258:
R1395-R1401,
1990
26.
Rowland, NE.
Effects of insulin and 2-deoxy-D-glucose on feeding in hamsters and gerbils.
Physiol Behav
21:
291-294,
1978[Medline].
27.
Rowland, NE,
Watkins L,
and
Carlton J.
Failure of 2-deoxy-D-glucose to stimulate feeding in deermice.
Physiol Behav
34:
155-157,
1985[Medline].
28.
Ruby, NF.
Paraventricular nucleus ablation disrupts daily torpor in Siberian hamsters.
Brain Res Bull
37:
193-198,
1995[ISI][Medline].
29.
Ruby, NF,
and
Zucker I.
Daily torpor in the absence of the suprachiasmatic nucleus in Siberian hamsters.
Am J Physiol Regulatory Integrative Comp Physiol
263:
R353-R362,
1992
30.
Ruf, T,
and
Heldmaier G.
Reduced locomotor activity following daily torpor in the Djungarian hamster: recovery from hypothermia?
Naturwissenschaften
79:
574-575,
1992[ISI][Medline].
31.
Ruf, T,
and
Heldmaier G.
Individual energetic strategies in winter-adapted Djungarian hamsters: the relation between daily torpor, locomotion, and food consumption.
In: Life in the Cold: Ecological, Physiological, and Molecular Mechanisms, edited by Carey C,
Florant GL,
Wunder BA,
and Horwitz B.. Oxford, UK: Westview, 1993, p. 99-107.
32.
Ruf, T,
Klingenspor M,
Preis H,
and
Heldmaier G.
Daily torpor in the Djungarian hamster (Phodopus sungorus): interactions with food intake, activity, and social behavior.
J Comp Physiol B
160:
609-615,
1991.
33.
Ruf, T,
Stieglitz A,
Steinlechner S,
Blank JL,
and
Heldmaier G.
Cold exposure and food restriction facilitate physiological response to short photoperiod in Djungarian hamsters (Phodopus sungorus).
J Exp Zool
267:
104-112,
1993[ISI][Medline].
34.
Schneider, JE,
Finnerty BC,
Swann JM,
and
Gabriel JM.
Glucoprivic treatments that induce anestrus, but do not affect food intake, increase fos-like immunoreactivity in the area postrema and nucleus of the solitary tract in Syrian hamsters.
Brain Res
698:
107-113,
1995[ISI][Medline].
35.
Schneider, JE,
Friedenson DG,
Hall AJ,
and
Wade GN.
Glucoprivation induces anestrus and lipoprivation may induce hibernation in Syrian hamsters.
Am J Physiol Regulatory Integrative Comp Physiol
264:
R573-R577,
1993
36.
Schneider, JE,
and
Zhu Y.
Caudal brain stem plays a role in metabolic control of estrous cycles in Syrian hamsters.
Brain Res
661:
70-74,
1994[ISI][Medline].
37.
Silverman, HJ.
Failure of 2-deoxy-D-glucose to increase feeding in the golden hamster.
Physiol Behav
21:
859-864,
1978[Medline].
38.
Stamper, JL,
and
Dark J.
Metabolic fuel availability influences thermoregulation in deermice (Peromyscus maniculatus).
Physiol Behav
61:
521-524,
1997[Medline].
39.
Stamper, JL,
Dark J,
and
Zucker I.
Photoperiod modulates torpor and food intake in Siberian hamsters challenged with metabolic inhibitors.
Physiol Behav
66:
113-118,
1999[Medline].
40.
Steinlechner, S,
Heldmaier G,
and
Becker H.
The seasonal cycle of body weight in the Djungarian hamster: photoperiodic control and the influence of starvation and melatonin.
Oecologia (Berl)
60:
401-405,
1983.
41.
Steinlechner, S,
Heldmaier G,
Weber C,
and
Ruf T.
Role of photoperiod: pineal gland interaction in torpor control.
In: Living in the Cold: Physiological and Biochemical Adaptations, edited by Heller HC,
Musacchia XJ,
and Wang LCH. New York: Elsevier, 1986, p. 301-307.
42.
Vitale, PM,
Darrow JM,
Duncan MJ,
Shustak CA,
and
Goldman BD.
Effects of photoperiod, pinealectomy and castration on body weight and daily torpor in Djungarian hamsters (Phodopus sungorus).
J Endocrinol
106:
367-375,
1985[Abstract].
43.
Weiner, J.
Limits of energy budget and tactics in energy investments during reproduction in the Djungarian hamster (Phodopus sungorus sungorus Pallas 1770).
Symp Zool Soc Lond
57:
167-187,
1987.
44.
Weiner, J,
and
Gorecki A.
Small mammals and their habitats in the arid steppe of central eastern Mongolia.
Polish Ecol Studies
8:
7-21,
1982.
This article has been cited by other articles:
|
|
 |
|
  K. M. Pelz, D. Routman, J. R. Driscoll, L. J. Kriegsfeld, and J. Dark Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R255 - R265. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
