Response accuracy and odor sampling time in mice trained to discriminate between enantiomers of carvone and those of terpinen-4-ol

Response accuracy and odor-sampling times were used to compare the ability of mice to detect (+)-carvone and (+)-terpinen-4-ol and to discriminate between enantiomers of carvone and of terpinen-4-ol. Except for increased odor sampling when mice were first exposed to the (+)-carvone odor, there was no difference in odor-sampling time or response accuracy in tests of odor detection or in discriminating between enantiomers of these odorants. These results fail to support the suggestion that odorants that produce different patterns of olfactory bulb activation should be easier to discriminate than those that produce much more similar patterns of bulbar activation.     

Hyperammonemia in anorectic tumor-bearing rats

Plasma ammonia concentrations were significantly elevated by 150% in anorectic rats bearing methylcholanthrene sarcomas. Assessment of ammonia levels in blood draining these sarcomas indicated nearly a 20-fold increase as compared with venous blood in control rats, suggesting the tumor mass as the source of this increase in ammonia. Infusing increasing concentrations of ammonium salts produced anorexia and alterations in brain amino acids in normal rats that were similar to those observed in anorectic tumor-bearing rats. Therefore, these results suggest that ammonia released by tumor tissue may be an important factor in the etiology of cancer anorexia.     

Comparison of the effects of fenfluramine and other anorectic agents in different feeding and drinking paradigms in rats

Fenfluramine (2.5 and 5 mg/kg) significantly suppressed the food intake of rats following food deprivation, administration of 2-deoxy-D-glucose (2DG), and during tail pressure. This suggests that fenfluramine has relatively general anorectic potency. Other "serotonergic" anorectics were studied for comparison. In a second experiment we determined that norfenfluramine and quipazine greatly suppressed food intake following food deprivation but, at the same doses, had relatively small effects on water intake following water deprivation. This was true for intraperitoneal and cerebroventricular routes of administration. The data have relevance for specificity of action of these agents and for the possible contribution of dopamine antagonist properties.     

Diminished hormonal responses to exercise in trained rats

Male rats (120 g) either were subjected to a 12-wk physical training program (T rats) or were sedentary controls (C rats). Subsequently the rats were killed at rest or after a 45- or 90-min forced swim. At rest, T rats had higher liver and muscle glycogen concentrations but lower plasma insulin. During exercise, blood glucose increased 60% in T rats but decreased 20% in C rats. Plasma glucagon and insulin concentrations did not change in T rats but plasma glucagon increased and insulin decreased markedly in C rats. Plasma epinephrine (90 min: range, 0.78-2.96 ng-ml-1, (T) vs. 4.42-15.67 (C)) and norepinephrine (90 min: 0.70-2.22 (T) vs. 2.50-6.10 (C)) were lower in T than in C rats. Hepatic glycogen decreased substantially and, as with muscle glycogen, the decrease was parallel in T and C rats. The plasma concentrations of free fatty acids were higher but lactate and alanine lower in T than in C rats. In trained rats the hormonal response to exercise is blunted partly due to higher glucose concentrations. In these rats adipose tissue sensitivity to catecholamines is increased, and changes in glucagon and insulin concentrations are not necessary for increased lipolysis and hepatic glycogen depletion during exercise.     

Ability to discriminate between related odor mixtures

The purpose of this study was to investigate (i) the abilityof human subjects to detect changes in related odor mixturesfollowing omission of components, and (ii) the possible relationshipbetween the number of substances comprising a mixture and theability to detect changes in its composition. A total of 36panelists was tested repeatedly in five separate sessions usingsniff bottles, and asked to rate the difference between pairsof stimuli using a 6-point verbal scale. Stimuli were 3-, 6-and 12-component mixtures paired with stimuli from which oneor more of the components had been omitted or had been leftunchanged. Rating behavior was highly consistent, with no significantdifferences found between sessions or panels in judging theidentical control pairs. Although asymmetrical pairs were judgedto be different significantly more often than control pairs,correct assignment was considerably poorer than expected. Correlationsbetween complexity of a stimulus and ability to discriminatechanges in its composition were weak and possibly confoundedby substance-specific, synergistic effects. While factors suchas lack of feedback or the arbitrary nature of the stimuli mayhave affected performance, it remains to be investigated whetherthe findings indeed reflect our limited capacity to discriminatebetween related odor mixtures.     

Magnesium and methionine deprivation affect the response of rats to boron deprivation

A series of nine experiments were done to obtain further evidence that boron might be involved in major mineral metabolism (Ca, P, and Mg), thus indicating that boron is an essential nutrient for animals. Eight factorially arranged experiments of 6–10 wk durations were done with weanling Sprague-Dawley male rats. One factorially arranged experiment was done with weanling spontaneously hypertensive rats. The variables in each experiment were dietary boron supplements of 0 and 3 μg/g, and dietary magnesium supplements of either 200 (Experiments 1–3) or 100 (Experiments 4–9) and 400 μg/g. In Experiments 7 and 9, a third variable was dietary manganese supplements of 25 and 50 μg/g. Methionine status was varied throughout the series of experiments by supplementing the casein-based diet with methionine and arginine. Findings were obtained indicating that the severity of magnesium deprivation and the methionine status of the rat strongly influence the extent and nature of the interaction between magnesium and boron, and the response to boron deprivation. When magnesium deprivation was severe enough to cause typical signs of deficiency, a significant interaction between boron and magnesium was found. Generally, the interaction was characterized by the deprivation of one of the elements making the deficiency signs of the other more marked. The interaction was most evident when the diet was not supplemented with methionine and especially when the diet contained luxuriant arginine. Signs of boron deprivation were also more marked and consistent when the diet contained marginal methionine and luxuriant arginine. Among the signs of boron deprivation exhibited by rats fed marginal methionine were depressed growth and bone magnesium concentration, and elevated spleen wt/body wt and kidney wt/body wt ratios. Because the boron supplement of 3 μg/g did not make the dietary intake of this element unusual, it seems likely that the response of the rats to dietary boron in the present study were manifestations of physiological, not pharmacological, actions, and support the hypothesis that boron is an essential nutrient for the rat. Mentions of a trademark or proprietary product does not consitute a guarantee or warranty of the product by the US Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.     

PEGylation of cholecystokinin prolongs its anorectic effect in rats

The anorectic compound CCK-9 was coupled to polyethylene glycol 5 kDa, 10 kDa, 20 kDa and 30 kDa, under different reaction conditions. Conjugates were purified by HPLC and characterized by MALDI-TOF MS. A 96% PEGylation yield was obtained in buffer pH 7.5 after 6h reaction at 20 degrees C. The anorectic activity was tested in vivo in rats. A single bolus intra-peritoneal injection of non-modified CCK-9 resulted in a significant initial food intake reduction 30 min after food presentation (87% compared to paired control group). When PEG-CCK-9 conjugates modified with polymers of molecular weight up to 20 kDa were injected, lower but statistically significant initial food intake reductions were obtained (76% for PEG 10 kDa-CCK-9 conjugate compared to control group). The cumulative food intake reduction of non-modified CCK-9 is normalized within 1-2h, whereas the PEG-CCK-9 molecules showed a prolonged anorectic activity lasting for 6h for PEG 5 kDa-CCK-9; 23 h for PEG 10 kDa-CCK-9 and between 8h and 23 h for PEG 20 kDa-CCK-9. For PEG 30 kDa-CCK-9 conjugate, neither an initial nor a cumulative FI reduction was observed. PEG-CCK-9 conjugates show a significantly prolonged anorectic activity in comparison to the non-modified peptide. This effect is most evident for the PEG 10 kDa-CCK-9 conjugate.     

Diminished satiation in rats exposed to elevated levels of endogenous or exogenous cholecystokinin

Rats maintained on a high-fat (HF) diet exhibit reduced sensitivity to the satiation-producing effect of exogenous CCK. Because more CCK is released in response to HF meals than low-fat (LF) meals, we hypothesized that increased circulating CCK associated with ingestion of HF diets contributes to the development of decreased CCK sensitivity. To test this hypothesis, we implanted osmotic minipumps filled with either NaCl or CCK octapeptide into the peritoneal cavity. Subsequently, we examined the effect of intraperitoneal NaCl or CCK (0.5 microg/kg) injection on 30-min food intake. CCK significantly reduced 30-min food intake less in rats implanted with CCK-releasing minipumps compared with those with NaCl-releasing minipumps. Because dietary protein is a potent releaser of endogenous CCK, we hypothesized that rats adapted to a high-protein (HP) diet might also exhibit reduced sensitivity to exogenous CCK. Therefore, in a second experiment, we examined CCK-induced reduction of food intake in rats maintained on LF and rats maintained on HF or HP. Ingestion of LF stimulates very little endogenous CCK secretion, whereas both HF and HP markedly increase plasma CCK concentrations. Both doses of CCK reduced food intake significantly less in HF and HP rats compared with LF rats. There were no differences in 24-h food intake, body weight, or body fat composition among LF-, HF-, and HP-fed rats. These results are consistent with the hypothesis that sustained elevation of CCK either by infusion of exogenous CCK or by dietary-induced elevation of plasma CCK contributes to the development of reduced sensitivity to exogenous CCK.     

Thermogenic and anorectic effects of ephedrine and congeners in mice and rats

(?)-Ephedrine has been shown to increase energy expenditure and cause the loss of body fat in rats and mice. The present study compares the effects of (?)- and (+)-ephedrine, (?)- and (+)- pseudoephedrine, (±)- and (+)-norephedrine and (?)- and (+)-norpseudoephedrine on food intake, energy expenditure and body composition in $\text{ob}$/$\text{ob}$ and normal mice and food intake in rats. The most potent anorectic and thermogenic compounds had the S configuration at the C-2 position but the orders of potencies for the compounds for anorexia and thermogenesis were not identical. The potencies of the compounds in reducing body lipid content correlated better with their thermogenic than their anorectic potencies.     

Hyperthermic and anorectic effects of oxazolidines derived from L-ephedrine in rats

Oxazolidines synthesized from (-) ephedrine have been proposed as potential pro-drugs, but no pharmacological data on these compounds has been yet reported. In this study, four such compounds are tested in rats for ephedrine-like activity using the hyperthermia and anorexia models. The compounds were synthesized by reaction of (-) ephedrine with salicylaldehyde, acetone, cyclohexanone, and benzaldehyde, respectively. The results showed that all of the compounds decreased food intake significantly, but only the acetone and the salicylaldehyde derivatives caused a significant elevation of body temperature. All of the compounds were less effective than (-) ephedrine in the anorexia model. The acetone and salicylaldehyde derivatives showed similar potency to (-) ephedrine in the hyperthermia model.     

How to discriminate between vibration syndrome and local fatigue of motorcyclists

Motorcyclists who work in some offices sometimes complained of coldness, pain and numbness of upper limbs. We studied how to discriminate between vibration syndrome and local fatigue of the motorcyclists. Subjects are 42 motorcyclists of an office in Aichi prefecture. 25 of them held several letters in their left hand when they delivered the letters. They complained of coldness, pain and numbness in the left upper limbs more than in the right limbs (p less than 0.01). We think that it is the local fatigue rather than the disorder of vibration syndrome that causes such symptoms. So it is very important to recognize the existence of local fatigue in order to know how to discriminate between vibration syndrome and local fatigue of the motorcyclists.     

Prostanoids counterbalance the synergism between endothelin-1 and angiotensin II in mesenteric veins of trained rats

Exercise-induced adaptations of the modulating mechanisms that influence the angiotensin (Ang II) responses assume different features depending on the venous bed. In femoral veins, exercise mobilizes vasodilator prostanoids to cooperate with NO in order to maintain reduced Ang II responses. On the other hand, exercise’s influence on the Ang II responses in veins that drain blood from the mesenteric region has been poorly described. Therefore, the present study aimed to identify the effects of a single bout of exercise, as well as exercise training, on the Ang II responses in mesenteric veins. The present study also aimed to investigate the involvement of prostanoids, NO and ET-1 in eventual exercise-induced modifications in these veins. To this end, mesenteric veins taken from resting-sedentary, exercised-sedentary, resting-trained and exercised-trained animals were studied in organ baths. In addition, the mRNA expression of prepro-endothelin-1 (ppET-1), as well as that of the ET_A and ET_B receptors, were quantified by real-time PCR in these veins. The results show that, either in absence or in presence of L-NAME, the Ang II responses were not different between groups. In the presence of indomethacin, higher Ang II responses were observed in the resting-trained animals than in the resting-sedentary animals. This difference, however, disappeared when L-NAME, BQ-123 or BQ-788 were added during incubation. In addition, no differences in ppET-1, ET_A or ET_B mRNA expression were observed between groups. Furthermore, in the presence of PD123,319, the Ang II responses in the exercised-sedentary animals were higher than those in the resting-sedentary animals. In conclusion, exercise training mobilizes endothelin-1 (ET-1) to reinforce the Ang II-induced responses mainly through ET_A activation. On the other hand, vasodilator prostanoids are mobilized to act in parallel with NO in order to counterbalance the Ang II responses that have been potentiated by ET-1 in these trained animals.     

Cytologic changes in the myocardia of rats trained to altitude hypoxia]

Rats trained to the high-altitude hypoxia displayed signs of intensification of both the plastic and lytic processes; one of these processes prevailed in different cells. There was no significant change in the mitochondrial and myofibrillar ratio. An increase of the relative volume of the microcirculatory bed on account of dilatation of small vessels without any increase of their count was noted.     

Effect of desmethylimipramine on tissue distribution and anorectic activity of chlorphentermine in rats

The anorectic effect and tissue distribution of chlorphentermine (CP) have been measured in the presence and absence of desmethyl-imipramine (DMI) in rats, following the finding that DMI was a potent displacer of CP from lung tissue in vitro. CP (10 mg/kg) produced significant anorexia for 4–5 hours after intraperitoneal administration and reduced food intake in a manner similar to that of fenfluramine; that is, CP decreased the rate of eating without affecting onset of eating. DMI caused dose-related changes in CP-induced anorexia; 5 mg/kg DMI inhibited the effects of CP (10 mg/kg) while, with 7.5 mg/kg DMI, there was potentiation. DMI (7.5 mg/kg) significantly (P<0.05) decreased CP (10 mg/kg) concentrations in lung tissue and increased concentrations in brain, liver and blood for up to four hours after treatment, but did not affect kidney or skeletal muscle levels. The CP tissue concentration-time profiles for liver, brain and kidney were significantly different in the presence and absence of DMI, suggesting non-linear kinetics, probably due to saturable tissue binding. Using a simple model to describe eating behaviour, the increased anorexia was found to be linearly related to the higher brain levels of CP seen in the presence of DMI.