Biomedical subjects

N E Rowland

Publications and source records attributed to N E Rowland.

At least 145 records · Page 8Linked to original sources

PubMed1986

Effects of dietary protein and tyrosine on behavior of diabetic rats.

Streptozotocin-diabetic and nondiabetic control male rats were fed synthetic diets varying in macronutrient content (experiment 1) or diets with or without added tyrosine (experiments 2 and 3). All rats were evaluated for stereotyped behaviors after administration of apomorphine (1 mg/kg) and amphetamine (3 and 5 mg/kg). At the end of experiments 2 and 3, rates of tyrosine hydroxylation in hypothalamus, nucleus accumbens, and striatum were determined by measuring L-3,4-dihydroxyphenylalanine concentrations after decarboxylase inhibition. In experiment 3 the ratios of tyrosine to dopamine were also measured in striatum and nucleus accumbens. Diabetic rats fed a standard high-carbohydrate diet showed decreased stereotypy relative to controls. Neither systematic alterations of fat or protein content of the diet nor selective tyrosine enrichment affected this attenuation of stereotypy in diabetics. L-3,4-dihydroxyphenylalanine concentration in nucleus accumbens was increased by dietary tyrosine enrichment in experiment 2 but not in experiment 3. However, brain tyrosine levels were elevated in rats fed tyrosine-enriched diets. These results argue against a significant contribution of precursor elevation to catecholamine function and behavior in experimental diabetes.

Animal Feed↗

PubMed1986

Insulin and metabolic efficiency in rats. I. Effects of sucrose feeding and BAT axotomy.

The role of insulin and brown adipose tissue (BAT) thermogenesis in metabolic efficiency (ME, the efficiency of body wt gain) was examined in rats with varied basal insulin status. Long-lasting insulin was administered using a protocol that did not alter food intake, yet increased ME in both groups. Half the rats were fed sucrose to stimulate BAT growth and thermogenesis. Insulin overrode the exaggerated decrease in ME in sucrose-fed diabetics, with only partial attenuation in controls. Interscapular BAT (IBAT) lipoprotein lipase activity was decreased in diabetic rats, restored by insulin treatment, and not affected in controls. Sucrose-fed diabetics and controls had their IBAT sham or bilaterally surgically denervated. Insulin decreased the thermogenic potential of BAT [cytochrome oxidase activity (COA)] in intact controls and diabetics; in the latter, insulin restored COA independent of BAT innervation. We conclude that insulin can increase ME without an associated increase in energy intake, regardless of basal insulin status, both insulin deficiency and excess decrease BAT thermogenic potential (COA), and hyperinsulinemia-induced increases in ME may result from decreased BAT mitochondrial proliferation.

Adipose Tissue, Brown↗

PubMed1986

Insulin and metabolic efficiency in rats. II. Effects of NE and cold exposure.

The role of insulin in metabolic efficiency (ME, i.e., efficiency of body wt gain) was examined under conditions of maximal energy expenditure in control and diabetic rats. Long-lasting insulin was administered using a protocol that did not affect food intake and increased ME in both groups. Half the animals were injected chronically with norepinephrine (NE). NE alone in controls decreased body weight and ME and increased brown adipose tissue (BAT) growth, thermogenic potential [cytochrome c oxidase activity (COA)], and lipoprotein lipases (LPL) activity; however, in diabetics, body weight, ME, and food intake all decreased and only BAT LPL activity and DNA content increased. The combination of NE and insulin increased BAT protein and COA in diabetics; in controls, all BAT measures were further increased and ME was intermediate to that of either treatment alone. Cold exposure decreased body weight and ME, increased food intake and qualitatively produced similar increases in BAT growth, COA, and LPL activity in both controls and diabetics. In diabetics, combined cold exposure and insulin did not affect the increase in BAT growth or LPL activity resulting from either treatment alone, but in controls this combination decreased BAT growth and COA. It is concluded that, even under conditions of maximal energy expenditure, both extremes of basal insulin status result in decreased BAT growth and thermogenic potential, but have opposite effects on ME.

Acclimatization↗

PubMed1985

Reduced dipsogenic responsiveness to intracerebroventricularly administered angiotensin II in estrogen-treated rats.

Chronic administration of two doses of estradiol benzoate (30 and 46 micrograms/kg/day) reduced the drinking response to acute administration of either isoproterenol (25 micrograms/kg, s.c.), the beta-adrenergic agonist, or angiotensin II (Ang II) (200 micrograms/kg, s.c.). The drinking response to intracerebroventricular administration of Ang II (40 ng/kg), but not carbachol (800 ng/kg), was also attenuated in estrogen-treated rats. An assessment of the Ang II binding in a diencephalic block of tissue from estrogen-treated rats revealed a significant reduction compared to untreated controls. The results suggest, but do not prove, that the reduced drinking response observed in estrogen-treated rats may be related to a reduction in the number of Ang II receptors in the brain.

Angiotensin II↗

PubMed1985

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.

Animals↗

PubMed1985

Ingestive behaviour of Syrian hamsters: advantages of the comparative approach.

A brief review of laboratory feeding studies in Syrian hamsters (Mesocricetus auratus) is presented. A number of profound behavioural differences between rats and hamsters are noted. One such difference concerns the diurnal organization of energy input and expenditure. It is suggested that several of these differences might be exploited at the level of neurochemical correlates of feeding, and some preliminary studies are summarized. Finally, some unexpected abnormalities in salt and water intake in regard to the actions of angiotensin II are identified as further areas for comparative investigation.

Animals↗

PubMed1985

Metabolic and neurochemical correlates of glucoprivic feeding.

Various hypotheses are reviewed concerning the mechanisms of feeding induced by insulin or 2DG. New data are presented to show that elevated plasma ketone levels are not sufficient to suppress 2DG feeding, suggesting that nourishment of the brain either does not occur or is not sufficient to stop 2DG feeding. We find that both acetoacetate and hydroxybutyrate suppress spontaneous feeding. Another series of studies investigated the effects of 2DG and insulin on catecholamine turnover in several brain regions of animals that do (rat, mouse) or do not (hamster) eat in response to these stimuli. The effects of glucoprivic stimuli on NE turnover were minimal; however, 2DG did appear to inhibit DA turnover, especially in nucleus accumbens. Thus, brain NE does not seem specifically involved in glucoprivic feeding, data which are supported by a lack of additivity of feeding induced by 2DG and by clonidine. Finally, to resolve some of the disparate data concerning the effects of glucose infusion on insulin-induced feeding, we examined the time course for effects on feeding and for glucose tolerance. It appears that glucose strongly inhibits feeding only when it is utilized.

Animals↗

PubMed1985

Nutritional influences on dietary selection patterns of obese and lean Zucker rats.

Little is known about the behavioral, nutritional, and metabolic events that control dietary intake quality. Two experiments are described that manipulate nutritional conditions that have been hypothesized to affect dietary item choice so as to assess what effect, if any, the added factor of genetic obesity has in modifying the response to these manipulations. In the first experiment, 5 week old male obese and lean Zucker rats were fed a diet that varied in protein content (10%, 20%, or 60% casein by weight) for ten weeks. They were then allowed to select a diet from three separate macronutrient sources (casein, starch, or corn oil). Although body weights at the end of the 10 week maintenance period were markedly different, selection patterns were not influenced by pre-feeding different levels of protein. Obese rats selected a diet that was higher in fat and lower in protein than the diets composed by lean rats. In the second experiment, four groups of 7 month old obese and lean Zucker rats were given access to one of four diets that varied in protein content (5%, 10%, 15%, or 20% casein by weight). In addition, each rat was periodically given access to a 32% sucrose solution. Access to sucrose promoted increases in total caloric intake, independent of the protein content of the diet. Obese rats typically ate more calories per day than did their lean littermates. Results from these experiments suggest that food item selection is determined more by factors associated with obesity than by factors associated with dietary history.

Animal Nutritional Physiological Phenomena↗

PubMed1985

Role of renin-angiotensin-aldosterone system in NaCl appetite of rats.

A variety of experimental paradigms is now known to induce an appetite for NaCl solutions in rats. These include 1) bilateral adrenalectomy; 2) hypothyroidism; 3) salivariectomy; and 4) administration of hydrochlorothiazide, metyrapone, estrogen, methylxanthines, captopril, propranolol, large doses of deoxycorticosterone acetate, and intraperitoneal isotonic glucose or subcutaneous polyethylene glycol. A point of commonality among these is that a reduction in preference threshold accompanies the appetite for NaCl in all cases thus far tested. An additional point is the fact that each paradigm inducing a salt appetite, except salivariectomy, can be linked to an effect on the renin-angiotensin-aldosterone system. The level of angiotensin II in the brain may play a role in the induction of a salt appetite in the rat. It is clear, however, that modest doses of mineralocorticoid hormones, given in conjunction with the stimulus producing the salt appetite (e.g., adrenalectomy, thyroidectomy, or treatment with captopril), reduces NaCl intake to control level. Although this effect can be partially explained in most cases by the consequent reduction in angiotensin II production, the salt appetite that occurs when mineralocorticoid concentration in blood is high and angiotensin II concentration is low, or when both are low, requires another explanation. This may be related to the effect of mineralocorticoid hormones on salivary sodium concentration. The role of the concentration of sodium in saliva on intake of NaCl solution provides an alternative explanation for the induction of a salt appetite in rats and merits additional study.

Adrenalectomy↗

PubMed1985

Nycthemeral rhythms and sodium chloride appetite in rats.

Adrenalectomized rats maintained on a 12:12 light-dark cycle drank large amounts of 0.3 M NaCl solution during the night. They showed virtually no NaCl appetite during the day. As a result of their high day natriuresis, the adrenalectomized rats sustained a negative Na+ balance during the day about three times that of controls. This was offset by a correspondingly higher positive Na+ balance at night. In a second experiment in intact rats, the latency to exhibit NaCl appetite during polyethylene glycol-induced hypovolemia was shorter when the treatment was administered in the evening than in the morning. This again demonstrates a relative facilitation of NaCl intake at night and suggests a major nycthemeral interaction with putative physiological stimuli of NaCl appetite.

Adrenalectomy↗

PubMed1985

Effect of chronic administration of deoxycorticosterone acetate on salt appetite of captopril-treated rats.

Chronic dietary administration of the angiotensin I-converting enzyme inhibitor, captopril (1.0 g/kg food), induced an appetite for 0.15 M NaCl solution relative to distilled water in a two-bottle ad libitum access paradigm. Graded doses of deoxycorticosterone acetate (DOCA) were administered to the captopril-treated rats via Silastic tubes implanted sc. A U-shaped dose-response relationship was observed between dose of DOCA and intake of 0.15 M NaCl solution. The lowest intake of NaCl occurred with a dose of 102.1 micrograms DOCA/day (333 micrograms/kg X day). Water and food intakes were not affected significantly. At the end of the first week of treatment with DOCA, pilocarpine (3.0 mg/kg, ip.)-stimulated salivary chloride concentration was measured. The relationship between salivary chloride concentration and mean intake of 0.15 M NaCl solution was also U shaped, with the minimal NaCl intake associated with a salivary chloride concentration of 54 meq/liter. During the second week of treatment with DOCA, all rats were offered a choice between 0.25 M NaCl solution and distilled water. Rats receiving DOCA at doses of 102.1 micrograms/day or greater had a significantly lower intake of NaCl solution than those receiving either captopril alone or 66.5 micrograms DOCA/day in combination with captopril. These results indicate that the appetite for NaCl solution induced by captopril can be inhibited by concurrent administration of DOCA. They also suggest that changes in the concentration of electrolytes in saliva may be associated with changes in the appetite for NaCl solution.

Animals↗

PubMed1984

Clonidine antagonism of angiotensin-related drinking: a central site of action.

Administration of either isoproterenol (25 micrograms/kg, s.c.) or angiotensin II (200 micrograms/kg, s.c.) induces drinking in rats within 0.5-1 h. This drinking was inhibited by prior administration of the presynaptic alpha-adrenergic agonist clonidine (12 micrograms/kg, i.p.). Urine output was enhanced by clonidine in the angiotensin II-, but not the isoproterenol-treated group. Drinking in response to peripheral administration of either angiotensin II or isoproterenol was also inhibited by intracerebroventricular (i.v.t.) administration of clonidine (8 micrograms/kg). This dose of clonidine also enhanced the urine output after angiotensin II. Further, the drinking induced by i.v.t. administration of angiotensin II, at 4 but not 20 ng/kg was inhibited by peripheral administration of clonidine (12 micrograms/kg, i.p.). When clonidine was administered i.v.t. prior to i.v.t. injection of either angiotensin II (20 ng/kg) or carbachol (1.2 micrograms/kg), the drinking response to these dipsogens was attenuated. These results suggest that clonidine may act centrally to attenuate drinking at a site, possibly in the nucleus tractus solitarius, that may be considered a final common pathway for this response.

Angiotensin II↗

PubMed1984

A role for presynaptic alpha 2-adrenoceptors in angiotensin II-induced drinking in rats.

Studies from this laboratory have shown that either central or peripheral administration of clonidine, the alpha 2-adrenoceptor agonist, can attenuate a variety of dipsogenic stimuli in rats. Further, yohimbine and tolazoline, alpha 2-adrenoceptor antagonists, augment the drinking response to both peripherally administered isoproterenol and angiotensin II. Studies reported here establish a dose-inhibition relationship between the dose of clonidine administered (2 to 32 micrograms/kg) intracerebroventricularly (IVT) and inhibition of the drinking response to peripherally administered angiotensin II (200 micrograms/kg. SC). DI50 was approximately 4 micrograms/kg. Yohimbine (300 micrograms/kg, SC) reversed the antidipsogenic effect of centrally administered clonidine (32 micrograms/kg, IVT) on angiotensin II-induced (200 micrograms/kg, SC) water intake. Phenylephrine, an alpha 2-adrenoceptor agonist, administered IVT (40 and 80 micrograms/kg) also inhibited angiotensin II-induced drinking in a dose-related fashion. The antidipsogenic effect of phenylephrine (80 micrograms/kg) was blocked by administration of yohimbine (300 micrograms/kg. SC). Thus, this effect of phenylephrine most likely occurs by way of alpha 2-adrenoceptors. These results support a role for the pre-synaptic alpha 2-adrenoceptor in the mediation of drinking in rats. Activation of alpha 2-adrenoceptors is accompanied by reduced water intake while inhibition of these receptors enhances water intake.

Angiotensin II↗

PubMed1984

Effect of intracerebroventricularly administered octopamines and synephrines on angiotensin II-induced water intake in rats.

Recent studies from this laboratory showed that l-m-synephrine (phenylephrine), a metabolite of l-m-octapamine, inhibited the drinking response of rats to peripherally administered angiotensin II. The objective of this investigation was to determine whether the isomers of both octapamine and synephrine could inhibit angiotensin II-induced dipsogenesis in the rat. Of the isomers tested, only d,l-m-octopamine and l-m-synephrine blocked the dipsogenic response to administration of angiotensin II (200 micrograms/kg, SC). The antidipsogenic effect of both d,l-m-octopamine and l-m-synephrine could be blocked by concurrent administration of yohimbine (300 micrograms/kg, IP), an alpha 2-adrenoceptor antagonist. The results indicate that m-octopamine and m-synephrine exert their antidipsogenic effect via alpha 2-adrenoceptors. These studies add to a growing body of data suggesting that activation of alpha 2-adrenoceptors inhibits, while blockade of these receptors enhances, angiotensin II-induced drinking.

2-Hydroxyphenethylamine↗

PubMed1983

Minireview. Stress induced eating.

The relationship of oral behaviors to stress has long been recognized both in humans and in wild animals. In the last decade numerous advances have been made in our understanding of stress-induced feeding predominately because of the development of the simple tail-pinch model of stress induced feeding in rats. Present evidence strongly implicates monoamines and the endogenous opioid peptides as well as other neuropeptides as playing a role in the central regulation of stress-induced eating.

Animals↗

PubMed1983

Diet selection and metabolic fuels in three models of diabetes mellitus.

Dietary self-selection and circulating metabolic fuels (glucose, free fatty acids, ketones) were examined in three forms of experimental diabetes mellitus in rats: pancreatectomy and streptozotocin treatment in adult and neonatal rats. Changes in diet selection resulting from insulin replacement also were examined. Differences were found in diet selection and circulating metabolic fuels between these types of diabetes. Mildly diabetic rats selected large amounts of fat while more severely diabetic rats primarily selected protein. Insulin treatment enhanced carbohydrate intake of diabetic rats and nearly normalized diet selection and circulating metabolic fuels. All diabetic groups exhibited severe glucose intolerance. These results support the observations of the beneficial effects of low-carbohydrate diets, question the generality of the use of high-fat diets, and suggest a more important role for high-protein diets in energy regulation in severely diabetic rats.

Animals↗

PubMed1983

On the mechanism of serotonin-induced dipsogenesis in the rat.

Subcutaneous administration of l-5-hydroxytryptophan (5-HTP), the precursor of serotonin, to female rats induces copious drinking accompanied by activation of the renin-angiotensin system. Neither a reduction in blood pressure nor body temperature accompanied administration of 5-HTP. The objective of the present study was to determine whether serotonin-induced dipsogenesis, like that of 5-HTP, is mediated via the renin-angiotensin system. Serotonin (2 mg/kg, SC)-induced drinking was inhibited by the dopaminergic antagonist, haloperidol (150 micrograms/kg, IP), which also inhibits angiotensin II-induced drinking. Both captopril (35 mg/kg, IP), an angiotensin converting enzyme inhibitor, and propranolol (6 mg/kg, IP), a beta-adrenergic antagonist, blocked serotonin-induced dipsogenesis. The alpha 2-adrenergic agonist, clonidine (6.25 micrograms/kg, SC), which suppresses renin release from the kidney, attenuated serotonin-induced water intake. The dipsogenic responses to submaximal concentrations of both serotonin (1 mg/kg, SC) and isoproterenol (8 micrograms/kg, SC) were additive rather than interactive suggesting that similar pathways mediate both responses. The serotonergic receptor antagonist, methysergide (3 mg/kg, IP), inhibited serotonin-induced drinking but had no effect on isoproterenol (25 micrograms/kg, SC)-induced dipsogenesis. However, neither serotonin (2 mg/kg, SC) nor isoproterenol (25 micrograms/kg, SC)-induced drinking was inhibited by cinanserin (25 micrograms/kg, IP). These data indicate that serotonin induces drinking in rats via the renin-angiotensin system. However, the results of the studies using methysergide suggest that serotonin appears to act at a point prior to activation of beta-adrenoceptors in the pathway leading to release of renin from the kidneys.

Animals↗

PubMed1983

Effects of yohimbine and tolazoline on isoproterenol and angiotensin II-induced water intake in rats.

Subcutaneous administration of the alpha 2-adrenoreceptor antagonists, yohimbine and tolazoline, at doses up to 1000 micrograms/kg, had no effect on water intake of female rats. However, when these compounds were administered SC in combination with either the beta-adrenoreceptor agonist, isoproterenol (10 to 25 micrograms/kg, SC), or with angiotensin II (200 micrograms/kg, SC), water intake was enhanced. In contrast, intraventricular administration of either tolazoline (10 and 20 micrograms/kg) or yohimbine (300 micrograms/kg) failed to augment the dipsogenic response to angiotensin II (150 micrograms/kg, SC). Thus, the enhancing effect of these alpha 2-adrenoreceptor antagonists on isoproterenol- and angiotensin II-induced water intakes appears to be manifested peripherally, rather than centrally. In view of the fact that clonidine, an alpha 2-adrenoreceptor agonist, has been shown to inhibit water intake induced by both isoproterenol and angiotensin II, the results suggest that the alpha 2-adrenoreceptor may play a role in modulating water intake induced by these two dipsogenic agents.

Angiotensin II↗