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Biomedical subjects

N Rowland

Publications and source records attributed to N Rowland.

At least 37 records · Page 2Linked to original sources

Nycthemeral variation in brain monoamines of Syrian hamsters: relation to activity and energy homeostasis.

No significant time-of-day variations were found in whole brain content of various monoamines and metabolites of sedentary Syrian hamsters. In a second experiment, norepinephrine and serotonin levels in diencephalon were higher in the morning than the evening of both sedentary and voluntarily exercising hamsters. In telencephalon, levels of most transmitters were elevated in the evening, with the most dramatic rises in the metabolites 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid. Again, in most instances, there was no difference between sedentary and exercise conditions.

Animals↗

Metabolic fuel homeostasis in Syrian hamsters: nycthemeral and exercise variables.

The food intake and growth of male and female golden hamsters, with and without access to running wheels, were measured under several conditions. These included different seasons, photoperiods and diets. Chow-fed males in wheels invariably had slowed weight gain and showed little hyperphagia relative to sedentary controls. One group of exercising female hamsters, fed high fat diet, grew faster than sedentary controls. The food intake of both exercising and sedentary groups was distributed evenly through the day/night cycle, but the exercising animals took smaller, more frequent meals at night. The nycthemeral variations in plasma glucose, triglycerides, free fatty acids and liver glycogen were quite small in sedentary hamsters. In exercising hamsters, however, liver glycogen was elevated in the late daytime and depleted in the mid-to-late night. In vivo lipogenesis rates in white and brown adipose and liver were elevated by day in the exercising compared to sedentary hamsters, and were lower at night in both groups. It appears that in exercising hamsters, and to a lesser extent sedentary hamsters, the day phase is one of inactivity and fuel storage, and the night phase is one of exercise and fuel mobilization.

Animals↗

Effects of chronic cold exposure on wheel running, food intake and fatty acid synthesis in Syrian hamsters.

Mesocricetus auratus with established wheel running in a thermoneutral environment (23 degrees C) showed an immediate suppression of running when placed in a cold room at 4 degrees C. This suppression was seen in three separate studies and lasted at least 1 month. Food intake of these hamsters rose within 48 hr in the cold, and body weight was maintained. In contrast, hamsters which had been sedentary in the 23 degrees C room showed a slower rise in food intake in the cold and sustained a chronic drop in body weight. In vivo fatty acid synthesis rates were greatly elevated in white and brown adipose tissue, but not liver, of exercise versus sedentary hamsters after 1 month in the cold, despite the relative inactivity of both groups throughout the cold exposure. Previous exercise training predisposes hamsters to efficient energy storage in the cold. The energy demand of the cold environment may be responsible for the decreased voluntary running.

Adipose Tissue↗

Anorexia and brain serotonin: development of tolerance to the effects of fenfluramine and quipazine in rats with serotonin-depleting lesions.

The acute and chronic effects of the "serotonergic anorectics" quipazine and dl-fenfluramine were examined in rats with substantial and specific depletions of brain 5-hydroxytryptamine (5-HT) induced by 5,7-dihydroxytryptamine (5,7-DHT). A "dessert" test which did not involve food deprivation was used to assess anorexia. Markedly increased sensitivity to the L-5-HTP-induced behavioral syndrome in 5,7-DHT-lesioned rats indicated postsynaptic 5-HT receptor supersensitivity. We found low (2 mg/kg) and intermediate (5 mg/kg) doses of fenfluramine, a putative presynaptic agent, were more effective in producing anorexia in lesion rats versus controls. A higher dose of fenfluramine (10 mg/kg) was less effective in lesion rats, suggesting that high dose and low dose fenfluramine anorexia are mediated by different mechanisms. We found quipazine, a putative 5-HT postsynaptic agonist, in a dose range of 2-10 mg/kg, to be no more effective in producing anorexia in lesion rats compared to controls. The development of tolerance to both fenfluramine and quipazine anorexia was similar for lesion and control rats showing that an intact brain 5-HT system is not necessary for tolerance. Tolerance to the "behavioral syndrome" induced by high doses of these agents developed rapidly in controls but not at all in lesion rats. This suggests that the behavioral syndrome and anorexia are independent effects of fenfluramine and quipazine. These results also challenge the popular notion that the primary anorectic action of fenfluramine is via brain serotonin.

5,7-Dihydroxytryptamine↗

Drinking: a final common pathway?

Administration of either naloxone, an opioid antagonist (1 mg/kg i.p.), or clonidine, an alpha 2 adrenoceptor agonist (12 micrograms/kg i.p.), attenuated the dipsogenic responses of female rats to both angiotensin II (200 micrograms/kg s.c.) and isoproterenol (25 micrograms/kg s.c.). The effect of simultaneous administration of naloxone and clonidine at these submaximal doses was an additive attenuation of both angiotensin II- and isoproterenol-induced water intakes. The absence of a significant interaction between naloxone and clonidine to inhibit drinking suggests that they act by a similar mechanism. Yohimbine, an alpha 2 adrenoceptor antagonist (300 micrograms/kg i.p.), administered in combination with naloxone, reversed the antidipsogenic effect on angiotensin II-induced drinking. These results provide further support for a role for alpha 2-adrenoceptors in laboratory-induced drinking in rats, and suggest the possibility that the antidipsogenic effect of naloxone is related to alpha 2 adrenergic mechanisms. A model to support these observations is presented in which two separate pathways for the induction of drinking (osmoreceptor- and angiotensin II-induced) converge on a final common pathway. Since both naloxone and clonidine inhibit responses to stimulation of both pathways for drinking, these results suggest that their actions are likely to be at some point as yet undetermined on the final common pathway.

Angiotensin II↗

Metabolic fuel homeostasis in golden hamsters: effects of fasting, refeeding, glucose, and insulin.

Experiments were conducted to investigate possible metabolic correlates of the unusual ingestive behavior of hamsters after food deprivation. A hypothesis of metabolic refractoriness predicts that hamsters, unlike rats, should not show changes in plasma metabolic fuels, adipose tissue, or liver after fasting and subsequent refeeding. This hypothesis was discredited by findings that fasted hamsters, like rats, have increased plasma ketones and free fatty acids and decreased liver glycogen. On refeeding, hamsters showed rapid reversal of these changes, with supranormal glycogen content and apparent fatty acid synthesis in liver. Additional studies examined the metabolic responses of hamsters and rats to exogenous insulin or glucose administration. Incorporation of 3H2O into liver fatty acids was greatly elevated in rats by both insulin and glucose, but in hamsters only insulin was effective. Some of these metabolic differences may help our understanding of the unusual refractoriness of hamster food intake to various stimuli.

Adipose Tissue↗

Towards a rationalization of counselling in general practice.

While there is good evidence to show that counselling may be beneficial to those patients in general practice with non-organic problems, deployment of the available resources lacks standardization and rationalization. The Counselling in Medical Settings Working Party of the British Association for Counselling is pressing for standardized training and accreditation of counsellors so that general practitioners will feel more confident about taking on workers who will ultimately be incorporated into the NHS team.

Counseling↗

Different behavioral mechanisms underlie tolerance to the anorectic effects of fenfluramine and quipazine.

Chronic administration of fenfluramine or quipazine before scheduled daily feeding sessions led to rapid and complete tolerance to the initial anorexia. Rats that received daily injections of fenfluramine after the daily meal also developed full tolerance. In contrast, quipazine administration after meals led to the development of little tolerance, indicating that quipazine tolerance appears to be learned or contingent. The implications of these data for neurochemical mechanisms of satiety are discussed.

Animals↗

Dietary self-selection in normal and diabetic rats after gastric loads of pure macronutrients.

Rats which were experimentally diabetic (streptozotocin, 45 or 70 mg/kg, or pancreatectomized) and their nondiabetic controls were allowed to select ad lib from three pure macronutrient sources of carbohydrate (CHO), protein, and fat. After full adaptation, the intakes were examined 2, 4, 6, and 24 hr following an intragastric load given at the end of the daytime. Noncaloric (control) or isocaloric loads of CHO or protein or fat were studied. Fat loads suppressed subsequent fat intake reasonably selectively; CHO and protein loads suppressed the intake of the corresponding macronutrient, but less selectively. There were no major qualitative differences between diabetic and nondiabetic rats.

Animals↗

Physiological and behavioral responses to glucoprivation in the golden hamster.

Golden hamsters failed to increase their food intake following food deprivation alone or in combination with insulin or 2-deoxy-D-glucose (2DG) treatment. 2DG also failed to induce feeding in hamsters tested at night. In this latter experiment, there was no effect of 2DG on wheel running or general alertness. Insulin administration significantly decreased plasma levels of glucose and free fatty acids (FFA). 2DG treatment produced a dose-related hyperglycemia associated with increased ketone levels. These data are discussed in terms of cerebral energy status and its relation to food intake and physiological responses.

Animals↗

Effect of chronic administration of fenfluramine and quipazine on body weight gain after ovariectomy and on brain serotonin receptor binding.

Chronic fenfluramine administration prevented excess weight gain following ovariectomy in rats but did not alter weight gain in sham-operated controls. Chronic quipazine treatment had no long-term effect on body weight. In one experiment, fenfluramine treatment for 28 days produced a 13% decrease in [3H]-serotonin binding to hypothalamic membranes and no change in [3H]-spiroperidol binding to striatum. In a second experiment, however, chronic fenfluramine had no effect on [3H]-serotonin binding to diencephalon. These results are discussed in terms of central and peripheral mechanisms of action and tolerance to fenfluramine.

Animals↗

Differences among 'serotonergic' anorectics in a cross-tolerance paradigm: do they all act on serotonin systems?

Rats on a 4 hr/day feeding schedule showed anorexia after i.p. injections of several 'serotonergic' agents. Tolerance developed within a few days of daily administration of all drugs except fluoxetine. The tolerant animals were then given a cross-tolerance test with a different agent, either the next day or after a drug free washout period. Rats which were tolerant to quipazine or MK 212 showed no cross-tolerance to fenfluramine or norfenfluramine. In contrast, rats which were tolerant to fenfluramine showed good cross-tolerance to quipazine or MK 212. However, after a washout period between the end of the chronic fenfluramine regimen and the cross-tolerance test, quipazine regained its full anorectic potency. The development of tolerance to fenfluramine was dependent upon the number of injections, not on their spacing. Fenfluramine-tolerant animals showed a partial decay of tolerance after a 3 day washout, but still retained some tolerance after 12 days. These findings imply that the mechanisms underlying the development of tolerance may differ from those which mediate its maintenance. Our data further suggest that not all of the agents act on the same neural system(s), and raise the possibility that non-serotonergic and/or non-cerebral systems may be involved in the mode of action of these agents.

Animals↗

Effects of dopamine-depleting brain lesions on experimental hyperphagia in rats.

Dopamine (DA)-depleting brain lesions of various sizes were produced in rats either by intracerebroventricular injections of 6-hydroxydopamine (6-HDA) or by electrolytic lesions of the lateral hypothalamic (LH) area. Among 30 animals that became aphagic and adipsic for at least four days after large LH or 6-HDA-induced brain lesions, only three developed hyperphagia after electrolytic lesions of the ventromedial hypothalamus (VMH) or daily injections of long-acting protamine-zinc insulin (PZI). In 20 rats with smaller LH or 6-HDA-induced lesions, which had not shown marked initial behavioral dysfunctions, only three gained as much weight after VMH lesions as the control animals. Similarly, 6 of 10 rats with smaller LH lesions could not tolerate a 15-day series of PZI treatments, although 14 of 17 rats with smaller 6-HDA-induced lesions increased their food intake and gained weight during the PZI treatments as did control animals. These results indicate that hypothalamic hyperphagia can be blocked by DA-depleting brain lesions that neither produce an initial period of aphagia and adipsia nor involve hypothalamic tissue. They further indicate that even small LH lesions may prevent the development of hyperphagia elicited by PZI, whereas only very large 6-HDA-induced lesions consistently have this effect.

Animals↗

Comparison of the suppression by naloxone of water intake induced in rats by hyperosmolarity, hypovolemia, and angiotensin.

The effect of naloxone upon water consumption by rats was assessed using two intensities each of IV NaCl (Hyperosmolarity), SC polyethylene glycol (hypovolemia), and IV angiotensin II. In each case naloxone produced a dose-related reduction in the amount drunk. Angiotensin-induced drinking was most easily inhibited, and was abolished by only 1 mg/kg naloxone. In contrast, 1 mg/kg naloxone produced only a 50% reduction NaCl-induced drinking, and hypovolemia-induced drinking was not completely reversed by 5 mg/kg. Naloxone was without effect upon the natriuresis after NaCl, or the hypertension during AII administrations. Parallels are drawn between the effects of naloxone on these types of thirst, and of other perturbations including brain damage and taste adulteration.

Angiotensin II↗

Naloxone suppresses insulin-induced food intake in novel and familiar environments, but does not affect hypoglycemia.

The opiate antagonist naloxone reduced the food intake induced in rats by acute injection of insulin. The suppression was most marked in the first hour after insulin injection. Insulin provoked less food intake when rats were tested in a novel environment compared with those tested in their home cage, but naloxone again significantly suppressed the intake in the first hour. Naloxone had no effect upon insulin-induced hypoglycemia.

Animals↗

Failure by deprived hamsters to increase food intake: some behavioral and physiological determinants.

A series of experiments was performed to further understand the behavioral and physiological determinants of postfast anorexia in golden hamsters. Postfast anorexia and/or the failure to adapt to a feeding schedule was not restricted to a particular photoperiod condition or strain of hamster. The anorexia was also observed with a liquid diet, but hamsters were able to show large increases in water intake on a water deprivation schedule. When the animals were group housed, they pouched food during scheduled feeds and ate it later: Meal size was not increased. Measures of gastric fill and plasma metabolites indicated that filling and emptying of the forestomach may occur with a periodicity similar to that of spontaneous meals, and the data were consistent with strong peripheral satiation/satiety mechanisms in this species.

Animals↗