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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bilateral 6-hydroxydopamine lesions of the nucleus accumbens septi (NAS) and olfactory tubercle (OT) caused enhanced intake of wet mash in 23-hr-food-deprived rats tested in photocell activity cages during restricted 30-min sessions. This mild hyperphagia was accompanied by a significant hypoactivity in the group with NAS/OT lesions. No hyperphagia was observed during a prolonged 120-min test session or in free-feeding tests conducted in the home cage. Anorexia induced by d-amphetamine (.5 and 1.5 mg/kg) was unaltered by the lesion, although the locomotor stimulant action of the drug was attenuated. A second experiment showed that the NAS/OT lesion also enhanced food intake in the photocell cages during 30-min sessions with dry food pellets but that food-associated drinking was concomitantly reduced. The results are consistent with the hypothesis that the behavioral changes caused by mesolimbic neuron destruction result in part from an inability to switch from one behavioral activity to another.
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PMID:Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat. 28 97

These experiments examine the acquisition of tail pinch-induced eating and responses to the anorectic agents d-amphetamine and d,l-fenfluramine by rats bearing N-methyl-D-aspartate (NMDA) lesions of the lateral hypothalamus. Lesioned rats lost weight following surgery but had no significant eating or drinking difficulties in the home cage (Clark et al. 1990). The acquisition of eating in response to tail pinch was enhanced in lateral hypothalamic-lesioned rats: they ate on earlier test sessions than controls and less pressure was required to elicit eating. Home cage food intake over the period when tail pinch was being examined was not affected by the lateral hypothalamic lesions. There were no significant differences between lateral hypothalamic-lesioned and control rats in terms of their anorectic responses to either d-amphetamine or d,l-fenfluramine, though the lesioned rats had a lower baseline intake. These data suggest that the lateral hypothalamus is not an important site for the mediation of amphetamine or fenfluramine anorexia but is involved in the acquisition of tail pinch-induced eating. The disinhibition of responding to tail pinch by lateral hypothalamic lesions is discussed in terms of the possible role the lateral hypothalamus plays in regulating cortical activity. The role of the medial hypothalamus and non-hypothalamic systems in the response to anorectic drugs and tail pinch is discussed.
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PMID:N-methyl-D-aspartate lesions of the lateral hypothalamus do not reduce amphetamine or fenfluramine anorexia but enhance the acquisition of eating in response to tail pinch in the rat. 136 34

Anorexia and cachexia are major problems in patients with cancer. Such measures as anti-cancer therapy, dietary counselling or hyperalimentation are not very successful in reversing this phenomenon in the vast majority of cancer patients. Thus, several drugs have been evaluated as agents to ameliorate cancer-associated anorexia/cachexia. Cyproheptadine is an antiserotonergic drug which appears to cause slight appetite stimulation in patients. A randomised clinical trial, however, was unable to demonstrate any weight gain from this agent. Corticosteroids are frequently used in clinical practice for appetite stimulation in patients with advanced malignancies. Supporting this practice, 4 randomised clinical trials showed that corticosteroid medications can stimulate the appetites of advanced cancer patients. However, these studies were not able to show any substantial nonfluid weight gain in treated patients. Megestrol acetate is a progestational agent which appears to be a relatively potent appetite stimulant. Randomised studies in advanced cancer patients have shown both substantial appetite stimulation and improvement in the nonfluid bodyweights of patients receiving this drug. Preliminary evidence also suggests that this drug has antiemetic properties. Several clinical studies are currently ongoing to determine the effect of various doses of megestrol acetate in patients with cancer. Efforts are also ongoing to evaluate both anabolic steroids and hydrazine sulfate as drugs for the treatment of patients with cancer anorexia/cachexia. The preliminary nature of these investigations, however, precludes recommendations for the use of either of these latter 2 drugs in routine clinical practice.
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PMID:Cancer-associated anorexia and cachexia. Implications for drug therapy. 137 16

The cause of cancer cachexia is unclear. Tumors may be competing with the host for ingested nutrients or may be releasing some factor that actively inhibits energy utilization. To explore these questions, plasma was sterilely collected and pooled from 103 terminally cachectic Fischer 344 rats implanted with an experimental sarcoma. Control plasma was collected in similar fashion from 138 nontumor-bearing rats (NTBP). Plasma from tumor-bearing rats (TBP) or NTBP was continuously infused in a randomized, blinded fashion for 4 days into 20 normal rats. During infusion, food intake and nitrogen excretion were measured daily. At sacrifice, body weight and organ masses were determined. Rats receiving TBP demonstrated an immediate and profound anorexia compared with those receiving NTBP. Total food intake during treatment was 31.2 +/- 3.3 (g +/- SEM) in the TBP group versus 48.2 +/- 2.8 in the NTBP group (P less than 0.001 by t test). Likewise, the total decline in body weight was greater in the TBP group as compared with the NTBP group (-35.2 +/- 3.4 versus -14.6 +/- 4.0, P less than 0.001). Mean daily nitrogen balance during treatment was negative in the rats receiving TBP (-14.5 +/- 20.1 mg +/- SEM) while remaining highly positive in the rats receiving NTBP (110.7 +/- 19.3, P less than 0.002). Finally, cardiac and gastrocnemius muscle masses were decreased, while hepatic mass was unaffected. These data demonstrate that the syndrome of cancer-associated cachexia is transmissible in plasma and therefore may be mediated by a circulating molecule or molecules. Identification and purification of the molecule(s) responsible for this effect would have obvious clinical benefits.
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PMID:Cancer cachexia is transmissible in plasma. 159 73

Preliminary information has suggested that megestrol acetate leads to appetite stimulation and nonfluid weight gain in patients with breast cancer, other cancers, and AIDS. Pursuant to this, we developed a randomized, double-blind, placebo-controlled trial of megestrol acetate in patients with cancer-associated anorexia and cachexia. We randomly assigned 133 eligible patients to receive 800 mg of megestrol acetate per day or a placebo. Patients assigned to megestrol acetate more frequently reported improved appetite (P = .003) and food intake (P = .009) when compared with patients receiving the placebo. A weight gain of 15 lb or more over baseline was seen in 11 of 67 (16%) patients receiving megestrol acetate compared with one of 66 (2%) given the placebo (P = .003). Patients receiving megestrol acetate reported significantly less nausea (13% vs. 38%; P = .001) and emesis (8% vs. 25%, P = .009). No clinically or statistically significant toxic reactions were ascribed to megestrol acetate, with the exception of mild edema. This study convincingly demonstrated that megestrol acetate can stimulate appetite and food intake in patients with anorexia and cachexia associated with cancer, leading to significant weight gain in a proportion of such patients.
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PMID:Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. 199 53

Changes in body weight and taste aversion in the learned helplessness paradigm were examined. In Experiment 1, adult male Sprague-Dawley rats drank saccharin or a control solution, followed by either 100 inescapable shocks or simple restraint. Rats were weighted daily and were tested for saccharin aversion two days after the stress session. Shocked rats gained less weight in the days after stress than restrained controls. Saccharin aversion was apparent only among rats that had consumed saccharin before the stress session. Experiment 2 examined whether control over shock affected body weight or taste aversion. Home-cage controls were included to assess the effects of restraint alone. In addition, the combined effects of shock and a toxin on aversion were studied. Rats drank saccharin solution, followed by escapable or inescapable shock, restraint, or no treatment. Then half of each group was injected with saline; the other half was injected with lithium chloride. As in Experiment 1, shock reduced body weight relative to restraint or no treatment, and shock produced a taste aversion among saline-treated rats. However, shock attenuated the aversion produced by lithium chloride, as did simple restraint. There were no differences in body weight or taste aversion between escapably and inescapably shocked rats. These results suggest a role for stress in the anorexia and weight loss associated with clinical depression and may have implications for theories of learning and learned helplessness.
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PMID:Stressors in the learned helplessness paradigm: effects on body weight and conditioned taste aversion in rats. 285 83

Cachectin/tumor necrosis factor (TNF) is a macrophage product which may have a role in cancer cachexia. Recombinant human cachectin/TNF (Cetus Corporation) was administered i.p. twice daily to male F344 rats at varying, nonlethal dosages for either 5 or 10 days, and daily rat food intake and body weight were measured. There was a dose-dependent cachectin/TNF-induced decline in food intake and body weight gain over the treatment period. However, after 1 day rats became tolerant to these effects and increased food intake and gained body weight despite receiving cachectin/TNF. Rats were subsequently inoculated with a transplantable methylcholanthrene-induced sarcoma, and survival was measured. Rats previously treated with high-dose (either 100 or 200 micrograms/kg/day) cachectin/TNF survived significantly longer following tumor inoculation than did control rats given saline or rats given 10 micrograms/kg/day of cachectin/TNF. Analysis of tumor growth curves and tumor weight indicated that high-dose cachectin pretreatment did not retard tumor growth. Analysis of food intake and tumor burden following tumor inoculation indicated that high-dose cachectin pretreatment decreased the reduction in food intake associated with progressive tumor growth and allowed rats to withstand a greater tumor burden at death. Rats immunized with low-dose human cachectin/TNF developed high IgG titers against human TNF, but failed to demonstrate the same protection against a methylcholanthrene-induced tumor challenge as rats made tolerant with repetitive twice daily high-dose cachectin/TNF. The observation of reduced cancer-associated anorexia and increased survival of tumor-bearing rats associated with previous tolerance to exogenous cachectin/TNF strengthens the contention that endogenously produced cachectin may be a factor in the pathogenesis of cancer anorexia in the tumor-bearing rat. The mechanism of this tolerance is unclear but does not appear to be a humoral immune response.
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PMID:Cachectin/tumor necrosis factor: a possible mediator of cancer anorexia in the rat. 316 53

Cancer cachexia describes a syndrome of progressive weight loss, anorexia, and persistent erosion of host body cell mass in response to a malignant growth. Although often associated with preterminal patients bearing disseminated disease, cachexia may be present in the early stages of tumor growth before any signs or symptoms of malignancy. A decline in food intake relative to energy expenditure (which may be increased, normal, or decreased) is the fundamental physiologic derangement leading to cancer-associated weight loss. In addition, abnormalities of host carbohydrate, protein, and fat metabolism lead to continued mobilization and ineffective repletion of host tissue, despite adequate nutritional support. Mediators of cancer anorexia and associated abnormalities are unknown. Cachectin/TNF or other host-derived cytokines (produced as a defense against malignancy) have been implicated as signal molecules in cachexia, based upon similar metabolic derangements produced by these cytokines in other chronic wasting illnesses. Nutritional support is effective in maintaining body weight of cachectic cancer patients, but ineffective in maintaining lean body mass. Although in one study parenteral nutritional support has improved operative morbidity and mortality in cancer patients, it has not yet improved response to chemotherapy or radiation therapy. Because of metabolic derangements seen in cancer cachexia, effective nutritional treatment regimens will probably require manipulation of host intermediary metabolism in addition to feeding. Insulin therapy or exercise are two such methods which appear to preserve host composition by preferential feeding of the host at the expense of the tumor. Future studies which more clearly define the role of signal molecules in producing cancer cachexia syndrome may lead to new treatment strategies, possibly involving modulation of the effects of such molecules on host metabolism.
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PMID:Cancer cachexia. 329 98

The hypothesis that epinephrine (EPI) and pancreatic glucagon (PG) inhibit feeding by activating a common physiological satiety mechanism was tested by comparing the two agents' behavioral effects. In several tests of specificity, EPI and PG had functionally different inhibitory actions. Intraperitoneal injection of 6.25-50 micrograms/kg EPI and 100-400 micrograms/kg PG elicited overlapping dose-related inhibitions of intake of milk diet in rats maintained ad lib on pelleted chow. Twenty-five to 50 micrograms/kg EPI also elicited anomalous behaviors that are not normally associated with feeding, including supine postures with limbs extended and crawling with trunk dorsoflexed and abdomen pressed against cage floor. EPI elicited similar anomalous behaviors in rats that either sham fed with open gastric cannulas, drank after water deprivation, or were presented neither food nor water. Fifty to 200 micrograms/kg EPI also inhibited water intake in the thirsty rats, and 25-50 micrograms/kg EPI inhibited sham feeding. PG, in contrast, neither elicited anomalous behaviors nor inhibited water intake nor inhibited sham feeding. These data demonstrate that the inhibitory actions of exogenous EPI and PG are functionally dissociable. We conclude that 25-200 micrograms/kg EPI acts nonspecifically to produce anorexia and adipsia, while PG elicits postprandial satiety.
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PMID:Epinephrine inhibits feeding nonspecifically in the rat. 361 47

To demonstrate that the anorexia and depletion of cachexia reverses on tumor removal, F344 rats underwent sarcoma resection when their food intake fell to 0 g/day. In survivors of surgery, reversal in food intake was apparent within 3 days postoperatively, followed after 2 days by gain in host weight. To detect whether the transmission of anorexia/cachexia in these tumor-bearing (TB) rats was via the circulation, four groups were studied: single non-tumor bearing (NTB); single TB; parabiotic NTB; and parabiotic TB. The measured blood exchange rate between parabiotic halves was 1.2-1.5%/min. No cachectic effect was detected in either half of the NTB parabionts. There was no evidence of sarcoma metastases in the tumor-free half of the parabiotic TB pair. All the rats associated with the presence of tumor showed cachectic effects but the degree and timing of effect varied among the three conditions, single TB, parabiotic TB half, and parabiotic tumor-free half. In all variables examined (fall in food intake, time of first fall in food intake, host weight loss, elevation of blood urea nitrogen) the severities were always in the same sequence: single TB greater than parabiotic TB half greater than parabiotic tumor-free half greater than NTB. In addition, the TB parabiotic pair had a significantly longer survival time and grew a significantly larger tumor than did the single TB animal. The parabiotic tumor had a slower initial growth rate and a slower deceleration rate than the singlet tumor. These results provide evidence for the humoral mediation of cancer-associated cachexia.
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PMID:Parabiotic transfer of cancer anorexia/cachexia in male rats. 386 7


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