Orexin-A does not stimulate food intake in old rats

2004 ◽  
Vol 287 (6) ◽  
pp. G1182-G1187 ◽  
Author(s):  
Saeko Takano ◽  
Setsuko Kanai ◽  
Hiroko Hosoya ◽  
Minoru Ohta ◽  
Hiroshi Uematsu ◽  
...  

Aging is associated with a progressive decrease in appetite and food intake. Both A and B orexins, expressed in specific neurons of the lateral hypothalamic area, have been implicated in the regulation of sleep and feeding. In this study, the stimulatory effect of intracerebroventricular administration of the orexins on food intake was compared between young (4-mo-old) and old (25- to 27-mo-old) male Wistar rats. A stainless steel cannula was implanted stereotactically into the left lateral ventricle. After a 7-day recovery period, different doses (0–30 nmol) of orexins were injected into the left lateral ventricle without anesthesia. Food and water consumptions were measured at 1, 2, and 4 h after injection. The protein levels of orexin receptors, a specific receptor for orexin-A (OX1R) and a receptor for both orexin-A and -B (OX2R), in the hypothalamus were determined by Western blot analysis and compared between young and old rats. Intracerebroventricular administration of orexin-A stimulated food intake in a dose-dependent manner in young rats. However, no effects were observed at any dose in old rats. The protein level of OX1R in the hypothalamus was significantly lower in old rats than in young rats, although the protein level of OX2R was comparable between groups. Results of the present study indicate that the function of the orexin system is diminished in old rats. The decrease in the OX1R protein level in the hypothalamus could be responsible for orexin-A's lack of stimulation of food intake in old rats.

Peptides ◽  
2011 ◽  
Vol 32 (7) ◽  
pp. 1357-1362 ◽  
Author(s):  
Eri Yokobori ◽  
Kenji Kojima ◽  
Morio Azuma ◽  
Ki Sung Kang ◽  
Sho Maejima ◽  
...  

1998 ◽  
Vol 79 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Isabelle Savary ◽  
Elisabeth Debras ◽  
Dominique Dardevet ◽  
Claire Sornet ◽  
Pierre Capitan ◽  
...  

This study was carried out to analyse glucocorticoid-induced muscle wasting and subsequent recovery in adult (6-8 months) and old (18-24 months) rats because the increased incidence of various disease states results in hypersecretion of glucocorticoids in ageing. Adult and old rats received dexamethasone in their drinking water for 5 or 6 d and were then allowed to recover for 3 or 7 d. As dexamethasone decreased food intake, all groups were pair-fed to dexamethasonetreated old rats (i.e. the group that had the lowest food intake). At the end of the treatment, adult and old rats showed significant increases in blood glucose and plasma insulin concentrations. This increase disappeared during the recovery period. Protein synthesis of different muscles was assessed in vivo by a flooding dose of [13C]valine injected subcutaneously 50 min before slaughter. Dexamethasone induced a significant decrease in protein synthesis in fast-twitch glycolytic and oxidative glycolytic muscles (gastrocnemius, tibialis anterior, extensor digitorum longus). The treatment affected mostly ribosomal efficiency. Adult dexamethasone-treated rats showed an increase in protein synthesis compared with their pair-fed controls during the recovery period whereas old rats did not. Dexamethasone also significantly decreased protein synthesis in the predominantly oxidative soleus muscle but only in old rats, and increased protein synthesis in the heart of adult but not of old rats. Thus, in skeletal muscle, the catabolic effect of dexamethasone is maintained or amplified during ageing whereas the anabolic effect in heart is depressed. These results are consistent with muscle atrophy occurring with ageing.


1998 ◽  
Vol 274 (4) ◽  
pp. E627-E633 ◽  
Author(s):  
David S. Ludwig ◽  
Kathleen G. Mountjoy ◽  
Jeffrey B. Tatro ◽  
Jennifer A. Gillette ◽  
Robert C. Frederich ◽  
...  

Melanin-concentrating hormone (MCH) and α-melanocyte-stimulating hormone (α-MSH) demonstrate opposite actions on skin coloration in teleost fish. Both peptides are present in the mammalian brain, although their specific physiological roles remain largely unknown. In this study, we examined the interactions between MCH and α-MSH after intracerebroventricular administration in rats. MCH increased food intake in a dose-dependent manner and lowered plasma glucocorticoid levels through a mechanism involving ACTH. In contrast, α-MSH decreased food intake and increased glucocorticoid levels. MCH, at a twofold molar excess, antagonized both actions of α-MSH. α-MSH, at a threefold molar excess, blocked the orexigenic properties of MCH. MCH did not block α-MSH binding or the ability of α-MSH to induce cAMP in cells expressing either the MC3 or MC4 receptor, the principal brain α-MSH receptor subtypes. These data suggest that MCH and α-MSH exert opposing and antagonistic influences on feeding behavior and the stress response and may function in a coordinate manner to regulate metabolism through a novel mechanism mediated in part by an MCH receptor.


1998 ◽  
Vol 275 (1) ◽  
pp. R174-R179 ◽  
Author(s):  
Mark C. Flynn ◽  
Thomas R. Scott ◽  
Thomas C. Pritchard ◽  
Carlos R. Plata-Salamán

OB protein (leptin) decreases food intake in a variety of species. Here we investigated the effects of the intracerebroventricular administration of recombinant murine OB protein on food consumption and meal parameters in Wistar rats maintained ad libitum. The intracerebroventricular administration of OB protein (0.56–3.5 μg/rat) decreased feeding in a dose-dependent manner. Computer analysis of meal parameters demonstrated that OB protein (3.5 μg/rat, n = 10) decreased nighttime meal size by 42%, whereas meal frequency and meal duration were unaffected. Derived analyses for the nighttime also showed that OB protein decreased the feeding rate (meal size/meal duration) by 30%, whereas the satiety ratio (intermeal intervals/meal size) increased by 100%. A similar profile was observed during the daytime and total daily periods. The intracerebroventricular administration of heat-inactivated OB protein (3.5 μg/rat, n = 10) had no effect on any meal parameter. The results show that OB protein administered intracerebroventricularly inhibits feeding through a specific reduction of meal size.


1987 ◽  
Vol 113 (3) ◽  
pp. 473-478 ◽  
Author(s):  
M. N. Sillence ◽  
R. G. Rodway

ABSTRACT Two inhibitors of adrenal steroidogenesis were examined to determine whether the growth rate of female rats could be improved by lowering circulating plasma corticosterone concentrations. The first inhibitor, etomidate, is a potent narcotic agent and was found to have no effect on plasma corticosterone and deoxycorticosterone (DOC) concentrations at sub-narcotic doses. Growth rate, food intake, food conversion efficiency and adrenal weight were also unaffected by the drug. The second inhibitor, metyrapone, was shown in acute studies to have two distinct actions. In 6-week-old female rats moderate doses of metyrapone (50 mg/kg) had a stimulatory action resulting in increased plasma DOC and corticosterone concentrations. Higher doses of metyrapone (150–300 mg/kg) were increasingly less selective, causing an increase in plasma concentration of DOC, but attenuating the increase in corticosterone concentration, presumably by inhibiting the 11β-hydroxylase enzyme which allows the conversion of DOC to corticosterone. In adult rats (>12 weeks old) the classical response to metyrapone was observed. Plasma DOC concentrations were increased, while corticosterone levels were reduced in a dose-dependent manner. In 5-week-old rats treated chronically, metyrapone (300 mg/kg) had no effect on plasma corticosterone, but increased plasma DOC concentration, depressed food intake and reduced growth rate. In 8-week-old rats treated chronically, the high dose of metyrapone (300 mg/kg) required to lower peak plasma corticosterone concentrations produced toxic effects resulting in the death of three animals. The remaining animals recovered rapidly, and gained more weight than controls over the final 6 days of the experiment. However, this experiment was terminated before the treated animals were able to catch up with the controls. Inverse correlations were found between both plasma corticosterone and DOC concentrations and growth rate, confirming that growth may be retarded by the glucocorticoids and that inhibition of their production may be of potential use in stimulating growth. Neither of the agents tested in the present study, however, are likely to be future candidates as growth promoters. J. Endocr. (1987) 113, 473–478


2003 ◽  
Vol 285 (5) ◽  
pp. H2091-H2098 ◽  
Author(s):  
Hideki Hayashi ◽  
Chikaya Omichi ◽  
Yasushi Miyauchi ◽  
William J. Mandel ◽  
Shien-Fong Lin ◽  
...  

The influence of nicotine in modulating vulnerability to atrial tachycardia and fibrillation (AT/AF) remains ill defined. The isolated hearts of six young (2–3 mo) and six old (22–24 mo) male Fischer 344 rats were Langendorff perfused at 5 ml/min with oxygenated Tyrode solution at 37°C, and the whole heart was also super-fused with warmed oxygenated Tyrode solution at 15 ml/min. Nicotine prolonged the interatrial conduction time and effective refractory period that were significantly ( P < 0.05) higher in the old than in the young rats in a concentration-dependent manner. Nicotine had a biphasic effect on burst atrial pacing-induced AT in both groups, increasing it at 10–30 ng/ml while decreasing it at 50–100 ng/ml ( P < 0.01). Nicotine at 10–100 ng/ml increased burst atrial pacing-induced AF in the young rats but suppressed it in the old rats ( P < 0.01). Optical mapping showed the presence of multiple independent wavefronts during AF and a single periodic large wavefront during AT in both groups. Nicotine, at concentrations found in the blood of smokers (30–85 ng/ml), exerts biphasic effects on inducible AT/AF in young rats and suppresses it in the old rats by causing high degrees of interatrial conduction block.


1999 ◽  
Vol 849 (1-2) ◽  
pp. 248-252 ◽  
Author(s):  
Akihiro Yamanaka ◽  
Takeshi Sakurai ◽  
Takuo Katsumoto ◽  
Masashi Yanagisawa ◽  
Katsutoshi Goto

2011 ◽  
Vol 106 (6) ◽  
pp. 3129-3135 ◽  
Author(s):  
Tadataka Tsuji ◽  
Takashi Yamamoto ◽  
Susumu Tanaka ◽  
Sanam Bakhshishayan ◽  
Mikihiko Kogo

The orexins (orexin-A and orexin-B) are neuropeptides that are secreted from neurons in the lateral hypothalamus and that participate in the regulation of feeding behavior. It remains to be determined, however, how the orexins exert their effects on feeding behavior, including masticatory movements. To this end, we analyzed food intake behavior and masticatory muscle activity using video analysis and electromyography (EMG) recording methods. The results showed that the cumulative food intake over 4 h was larger in rats intraventricularly injected with either orexin-A or orexin-B than in saline-injected control rats. The latency to eating and the feeding time for a fixed amount of pellets were shortened by injections of orexins in a dose-dependent manner, with a more potent effect by orexin-A than orexin-B. The shorter feeding time corresponded to a decreased number of chewing cycles. EMG recordings from both the digastric and masseter muscles showed two distinct patterns of bursts corresponding to the gnawing and chewing phases. After the injection of orexin-A, the magnitude of the bursts became larger in both phases in the masseter muscle, the burst duration became longer in the chewing phase in the masseter muscle, and the interburst interval became shortened in the gnawing phase in both muscles. Consequently, the burst frequency in the chewing phase was increased in the digastric muscle and, conversely, reduced in the masseter muscle. These results suggest that the orexin-A-induced facilitatory feeding behavior is characterized by a dynamic jaw-opener activity that opens the mouth rapidly and a powerful jaw-closer activity for crushing the increased amount of food taken into the mouth. The possible involvement of orexin-A in binge eating disorder is discussed.


1975 ◽  
Vol 66 (1) ◽  
pp. 45-51 ◽  
Author(s):  
C. J. SHAAR ◽  
J. S. EUKER ◽  
G. D. RIEGLE ◽  
J. MEITES

SUMMARY Changes in serum LH and prolactin concentrations in response to bilateral gonadectomy and gonadal steroid replacement were measured in mature young (4–6 months) and old (23–30 months) female and male Long–Evans rats. On day 13 after gonadectomy, female rats were injected with oestradiol benzoate (OB) and male rats with testosterone propionate (TP) for a period of 12 days. They were then permitted a recovery period of 6 weeks. Serum prolactin and LH concentrations were measured by radioimmunoassay in single blood samples taken at various intervals before and after gonadectomy and during and after steroid treatment. Serum LH levels were about the same in intact young and old female rats, but after ovariectomy LH rose several fold higher in young than in old female rats. In male rats, serum LH values were about four times greater in intact young than in intact old rats, and after orchidectomy the increase in serum LH was greater in young than in old rats. Oestradiol benzoate and TP injections into female and male young and old rats produced variable effects on LH release. Serum prolactin concentrations were approximately six times higher in old intact than in young intact female rats, and after ovariectomy showed a much greater percentage reduction in old than in young female rats. Administration of OB produced a greater absolute increase in serum prolactin in old than in young female rats. Serum prolactin values were about the same in old and young male rats, and the effects of castration and TP administration on serum prolactin were not markedly different in the two age groups. These results indicate that old female and male rats are less capable of releasing LH than young rats of both sexes, but old females release more prolactin than young females.


1990 ◽  
Vol 122 (2) ◽  
pp. 191-200 ◽  
Author(s):  
C. G. J. Sweep ◽  
Margreet D. Boomkamp ◽  
István Barna ◽  
A. Willeke Logtenberg ◽  
Victor M. Wiegant

Abstract The effect of intracerebroventricular (lateral ventricle) administration of arginine8-vasopressin (AVP) on the concentration of β-endorphin immunoreactivity in the cerebrospinal fluid obtained from the cisterna magna was studied in rats. A decrease was observed 5 min following injection of 0.9 fmol AVP. No statistically significant changes were found 5 min after intracerebroventricular treatment of rats with 0.09 or 9 fmol. The decrease induced by 0.9 fmol AVP was of short duration and was found 5 min after treatment but not 10 and 20 min. Desglycinamide9-AVP (0.97 fmol), [pGlu4, Cyt6]-AVP-(4–9) (1.44 fmol), Nα-acetyl-AVP (0.88 fmol), lysine8-vasopressin (0.94 fmol) and oxytocin (1 fmol) when intracerebroventricularly injected did not affect the levels of β-endorphin immunoreactivity in the cerebrospinal fluid 5 min later. This suggests that the intact AVP-(1–9) molecule is required for this effect. Intracerebroventricular pretreatment of rats with the vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (8.63 fmol) completely blocked the effect of AVP (0.9 fmol). In order to investigate further the underlying mechanism, the effect of AVP on the disappearance from the cerebrospinal fluid of exogenously applied β-endorphin was determined. Following intracerebroventricular injection of 1.46 pmol camel β-endorphin-(1–31), the β-endorphin immunoreactivity levels in the cisternal cerebrospinal fluid increased rapidly, and reached peak values at 10 min. The disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid then followed a biphasic pattern with calculated half-lifes of 28 and 131 min for the initial and the terminal phase, respectively. Treatment of rats with AVP (0.9 fmol; icv) during either phase (10, 30, 55 min following intracerebroventricular administration of 1.46 pmol β-endorphin-(1–31)) significantly enhanced the disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid. The data suggest that vasopressin plays a role in the regulation of β-endorphin levels in the cerebrospinal fluid by modulating clearance mechanisms via V1-receptors in the brain.


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