American Journal of Physiology - Regulatory Integrative and Comparative Physiology
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The anorectic effect of fenfluramine is influenced by sex and stage of the estrous cycle in rats The controls of food intake differ in male and female rats. Daily food intake is typically greater in male rats, relative to female rats, and a decrease in food intake, coincident with the estrous stage of the ovarian reproductive cycle, is well documented in female rats. This estrous-related decrease in food intake has been attributed to a transient increase in the female rat's sensitivity to satiety signals generated during feeding bouts. Here, we investigated whether sex or stage of the estrous cycle modulate the satiety signal generated by fenfluramine, a potent serotonin (5-HT) releasing agent. To examine this hypothesis, food intake was monitored in male, diestrous female, and estrous female rats after intraperitoneal injections of 0, 0.25, and 1.0 mg/kg d-fenfluramine. The lower dose of fenfluramine decreased food intake only in diestrous and estrous females, suggesting that the minimally effective anorectic dose of fenfluramine is lower in female rats, relative to male rats. Although the larger dose of fenfluramine decreased food intake in both sexes, the duration of anorexia was greater in diestrous and estrous female rats, relative to male rats. Moreover, the magnitude of the anorectic effect of the larger dose of fenfluramine was greatest in estrous rats, intermediate in diestrous rats, and least in male rats. Thus our findings indicate that the anorectic effect of fenfluramine is modulated by gonadal hormone status.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 288 Số 6 - Trang R1486-R1491 - 2005
Intraventricular melanin-concentrating hormone stimulates water intake independent of food intake The lateral hypothalamus (LH) has a critical role in the control of feeding and drinking. Melanin-concentrating hormone (MCH) is an orexigenic peptidergic neurotransmitter produced primarily in the LH, and agouti-related protein (AgRP) is an orexigenic peptidergic neurotransmitter produced exclusively in the arcuate (ARC), an area that innervates the LH. We assessed drinking and eating after third ventricular (i3vt) administration of MCH and AgRP. MCH (2.5, 5, and 10 μg i3vt) significantly increased food as well as water intake over 4 h when administered during either the light or the dark portion of the day-night cycle. When MCH (5 μg) was administered to rats with access to water but no food, they drank significantly more water than when given the vehicle. AgRP (7 μg i3vt), on the other hand, increased water intake but only in proportion to food intake during the dark and the light, and water intake was not increased after i3vt AgRP in the absence of food. Hence, in contrast to AgRP, MCH elicits increased water intake independent of food intake. These results are consistent with historical data linking activity of the LH with water as well as food intake.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 284 Số 2 - Trang R494-R499 - 2003
Estradiol increases glucagon's satiating potency in ovariectomized rats Estradiol decreases meal size, food intake, and body weight in female rats. To investigate whether these effects of estradiol involve a change in the sensitivity of the signaling pathway through which pancreatic glucagon released during meals contributes to meal termination (satiation), glucagon or glucagon antibodies were infused via the hepatic portal vein in ovariectomized rats that were chronically treated with estradiol benzoate (2 μg/day sc) or vehicle alone (100 μl sesame oil). Infusions began at 1 h after dark onset, as rats were refed after 7 h of food deprivation. Glucagon (3 μg/min for 30 min) decreased feeding during the initial 45 min of food access in both groups of rats, but the inhibition was significantly greater in estradiol- than in oil-treated rats. Similarly, antagonism of endogenous glucagon by infusion of glucagon antibodies (a dose neutralizing 3 ng of glucagon in vitro during the first 3 min of refeeding) increased feeding significantly more in estradiol- than in oil-treated rats. These data indicate that an increase in the activity of the endogenous glucagon satiation-signaling pathway may be part of the mechanism for estradiol's inhibitory effect on feeding.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 281 Số 4 - Trang R1290-R1294 - 2001
Mice with MCH ablation resist diet-induced obesity through strain-specific mechanisms Genetics and environment contribute to the development of obesity, in both humans and rodents. However, the potential interaction between genes important in energy balance, strain background, and dietary environment has been only minimally explored. We investigated the effects of genetic ablation of melanin-concentrating hormone (MCH), a neuropeptide with a key role in energy balance, with chow and a high-fat diet (HFD) in two different mouse strains, one obesity-prone (C57BL/6) and the other obesity-resistant (129). Substantial differences were seen in wild-type (WT) animals of different strains. 129 animals had significantly lower levels of spontaneous locomotor activity than C57BL/6; however, 129 mice gained less weight on both chow and HFD. In both strains, deletion of MCH led to attenuated weight gain compared with WT counterparts, an effect secondary to increased energy expenditure. In both strains, feeding a HFD led to further increases in energy expenditure in both WT and MCH-KO mice; however, this increase was more pronounced in 129 mice. In addition, mice lacking MCH have a phenotype of increased locomotor activity, an effect also seen in both strains. The relative increase in activity in MCH−/− mice is modest in animals fed chow but increases substantially when animals are placed on HFD. These studies reinforce the important role of MCH in energy homeostasis and indicate that MCH is a plausible target for antiobesity therapy.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 289 Số 1 - Trang R117-R124 - 2005
Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1−/− mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1−/− mice demonstrated a significantly increased heart rate [24-h period: wild type 495 ± 4 vs. MCHR1−/− 561 ± 8 beats/min ( P < 0.001); dark phase: wild type 506 ± 8 vs. MCHR1−/− 582 ± 9 beats/min ( P < 0.001); light phase: wild type 484 ± 13 vs. MCHR1−/− 539 ± 9 beats/min ( P < 0.005)] with no significant difference in mean arterial pressure [wild type 110 ± 0.3 vs. MCHR1−/− 113 ± 0.4 mmHg ( P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1−/− mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1−/− mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1−/− mice, suggesting an increased sympathetic tone.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 287 Số 4 - Trang R749-R758 - 2004
The effects of selective and nonselective cyclooxygenase inhibitors on endothelin-1-induced fever in rats It was previously shown that sustained fever can be induced in rats by central injection of endothelin-1 (ET-1). This peptide appears to participate in the mechanism(s) of LPS-induced fever, which is reduced by pretreatments with ETB receptor antagonists. In this study, we compared the effects of a nonselective cyclooxygenase (COX) inhibitor, indomethacin, with those of two selective COX-2 inhibitors, celecoxib and lumiracoxib, on ET-1-induced fever in rats. Fever induced in conscious animals by ET-1 (1 pmol icv) or LPS (5 μg/kg iv) was prevented by pretreatments with celecoxib (5 and 10 mg/kg) or lumiracoxib (5 mg/kg) given by oral gavage 1 h before stimuli. Lower doses of celecoxib had partial (2.5 mg/kg) or no effect (1 mg/kg). Indomethacin (2 mg/kg ip) partially inhibited fever induced by LPS but had no effect on ET-1-induced fever. The levels of PGE2 and PGF2α in the cerebrospinal fluid (CSF) of pentobarbital sodium-anesthetized rats were significantly increased 3 h after the injection of LPS or ET-1. The latter increase was abolished by celecoxib at all tested doses and by indomethacin. In conclusion, selective COX-2 inhibitors were able to prevent ET-1-induced fever, indicating a role for COX-2 in this phenomenon. However, the fact that reduced CSF PG levels obtained with indomethacin and a low dose of celecoxib are not accompanied by changes in fever induced by ET-1, along with the lack of inhibitory effects of indomethacin on ET-1 fever, suggests that the latter might also involve COX-2-independent mechanisms.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 288 Số 3 - Trang R671-R677 - 2005
Sex differences in inflammation and inflammatory pain in cyclooxygenase-deficient mice There are two cyclooxygenase (COX) genes encoding characterized enzymes, COX-1 and COX-2. Nonsteroidal anti-inflammatory drugs are commonly used as analgesics in inflammatory arthritis, and these often inhibit both cyclooxygenases. Recently, inhibitors of COX-2 have been used in the treatment of inflammatory arthritis, as this isoform is thought to be critical in inflammation and pain. The objective of this study was to determine the effect of COX-1 or COX-2 gene disruption on the development of chronic Freund’s adjuvant-induced arthritis and inflammatory pain in male and female mice. The effect of COX-1 or COX-2 gene disruption on inflammatory hyperalgesia, allodynia, inflammatory edema, and arthritic joint destruction was studied. COX-2 knockout mice (COX-2 −/−) showed reduced edema and joint destruction in female, but not male, animals. In addition, neither male nor female COX-2 −/− mice developed thermal hyperalgesia or mechanical allodynia, either ipsilateral or contralateral to the inflammation. COX-1 gene disruption also reduced inflammatory edema and joint destruction in female, but not male mice, although females of both COX −/− lines did show some bony destruction. There was no difference in ipsilateral allodynia between COX-1 knockout and wild-type animals, but female COX-1 −/− mice showed reduced contralateral allodynia compared with male COX-1 −/− or wild-type mice. These data show that the gene products of both COX genes contribute to pain and local inflammation in inflammatory arthritis. There are sex differences in some of these effects, and this suggests that the effects of COX inhibitors may be sex dependent.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 291 Số 2 - Trang R327-R334 - 2006
Does experimental pain response vary across the menstrual cycle? A methodological review The findings on sex differences in human experimental pain research are inconsistent. One possible factor contributing to the inconsistent findings is the female hormonal cycle, as hormone levels may affect pain sensitivity. A number of studies suggest that women's responses to experimentally evoked pain vary across the menstrual cycle. However, at least an equal number of studies suggest a lack of variability. The purpose of this article is to review the literature with emphasis on what we believe could be the reasons for the inconsistent findings, namely, differences in populations sampled, timing of experimental sessions across the menstrual cycle, and nomenclature used to identify the time (phases) in the cycle when measurements were done, nature of the pain stimuli chosen, and outcomes measured. These inconsistencies and other methodological problems associated with most experimental pain studies make it difficult to draw inferences from this literature. For the science to improve, replication of significant findings using standardized timing of sessions, pain stimulus procedures, outcomes, and hormonal assessment is necessary.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 291 Số 2 - Trang R245-R256 - 2006
Locomotor muscle fatigue increases cardiorespiratory responses and reduces performance during intense cycling exercise independently from metabolic stress Locomotor muscle fatigue, defined as an exercise-induced reduction in maximal voluntary force, occurs during prolonged exercise, but its effects on cardiorespiratory responses and exercise performance are unknown. In this investigation, a significant reduction in locomotor muscle force (−18%, P < 0.05) was isolated from the metabolic stress usually associated with fatiguing exercise using a 100-drop-jumps protocol consisting of one jump every 20 s from a 40-cm-high platform. The effect of this treatment on time to exhaustion during high-intensity constant-power cycling was measured in study 1 ( n = 10). In study 2 ( n = 14), test duration (871 ± 280 s) was matched between fatigue and control condition (rest). In study 1, locomotor muscle fatigue caused a significant curtailment in time to exhaustion (636 ± 278 s) compared with control (750 ± 281 s) ( P = 0.003) and increased cardiac output. Breathing frequency was significantly higher in the fatigue condition in both studies despite similar oxygen consumption and blood lactate accumulation. In study 2, high-intensity cycling did not induce further fatigue to eccentrically-fatigued locomotor muscles. In both studies, there was a significant increase in heart rate in the fatigue condition, and perceived exertion was significantly increased in study 2 compared with control. These results suggest that locomotor muscle fatigue has a significant influence on cardiorespiratory responses and exercise performance during high-intensity cycling independently from metabolic stress. These effects seem to be mediated by the increased central motor command and perception of effort required to exercise with weaker locomotor muscles.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 294 Số 3 - Trang R874-R883 - 2008
Micropuncture studies of the osmoregulation in the nauplius of Artemia salina The osmoregulation of the nauplius of the brine shrimp, Artemia salina, was investigated using micropuncture and microanalytical techniques. The naupliar body fluid, hemolymph was hyposmotic to and had lower Na concentrations than the suspending medium for the range of medium salinities from 80 to 4,900 mM NaCl. In medium containing 20 mM NaCl, the hemolymph was hyperosmotic to the medium, with osmolarity of 101 +/- 8 mosmol/1 and with [Na] of 49 +/- 11 meq/1. Whereas the maximal observed NaCl concentration gradient between hemolymph and medium was 4,785 mM, during the incubation of nauplii in artificial seawater (osmolarity: 932 mosmol/1; and [Na]: 502 meq/1) the osmolarity and [Na] of the naupliar hemolymph were 161 +/- SD 16 mosmol/1 and 86 +/- 14 meq/1, respectively. The influx and efflux of Na between medium and hemolymph were measured using 22Na. The fluxes of this ion were temperature dependent. The main site of efflux of 22Na was the neck organ as was shown by experiments of differential recovery of 22Na introduced in the hemolymph. These studies demonstrate that the nauplius of A. salina has the ability to osmoregulate not only against high environmental salinities but also against low salinities approaching those of freshwater.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 234 Số 5 - Trang R216-R222 - 1978
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