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Biomedical subjects

D C Roberts

Publications and source records attributed to D C Roberts.

16 recordsLinked to original sources

Plasma lipoprotein changes in suckling and weanling rabbits fed semipurified diets.

The distribution and composition of the plasma lipoproteins were studied in suckling rabbits and in rabbits either weaned to or fed as young adults cholesterol-free, semipurified diets containing protein of animal (casein) or plant (soy protein isolate) origin. The raised cholesterol levels of the suckling period resulted in an increase of very low density and intermediate density lipoproteins in a making similar to that seen in adult rabbits fed a high fat diet supplemented with cholesterol. Young rabbits fed the cholesterol-free, semipurified, diet containing casein also became hypercholesterolemic but, in this case, the increased cholesterol was found primarily in lipoproteins of intermediate density. Cholesterol levels remained low in those rabbits fed the soy protein isolate diet, and the lipoprotein distribution was somewhat similar to that of chow-fed animals. It appears that the raised cholesterol levels during the suckling period result in different lipoprotein patterns to those produced in young adult animals by a cholesterol-free, semipurified diet.

Aging

Interaction of brain noradrenaline and the pituitary-adrenal axis in learning and extinction.

The effect of 6-hydroxydopamine-induced degeneration of the dorsal tegmental noradrenergic (NA) projection alone or in combination with the removal of the adrenal glands was examined on several behavioral tasks. No impairment of acquisition on a continuously reinforced lever pressing response for food reward was seen as a result of the combined treatment. However, resistance to extinction was observed after depletion of forebrain noradrenaline on its own and this effect was prevented by the adrenalectomy. Adrenalectomy on its own failed to affect extinction. Acquisition of a passive avoidance task was slightly impaired after forebrain noradrenaline depletion but only the group with combined noradrenaline loss and adrenalectomy showed a 24 hour retention deficit. No alteration in shock thresholds was found in any group although both adrenalectomized groups consumed less food and were slightly less active in locomotor cages. It is suggested that previous reports of acquisition and retention deficits in avoidance tasks after combined dorsal NA bundle lesions and adrenalectomy are due to alterations in fear motivation rather than to a general learning impairment.

Animals

Behavioural effects of 6-hydroxydopamine-induced depletion of spinal noradrenaline.

Bilateral injection of 6-hydroxydopamine (4 micrograms/2 microL) into the caudal medulla of rats reduced spinal noradrenaline (NA) to 6% of control values. No significant NA depletion was observed in the hippocampus, cortex, or cerebellum, and a small loss of NA was found in the hypothalamus. These lesions were found to elevate significantly threshold shock levels necessary to elicit jump responses, and they also abolished the reflexive alternating motor movements produced by decapitation. These data support the hypothesis that spinal NA mechanisms modulate reflexive motor movements. However, no significant effect of these lesions was found on either spontaneous or amphetamine-induced locomotor activity, suggesting that spinal NA does not play a significant role in these behaviours.

Amphetamine

Influence of diet on plasma cholesterol concentrations in suckling and weanling rabbits.

Rabbits were weaned to different semipurified diets to determine which characteristics of the diet were required to maintain the hypercholesterolemia of the suckling period. Gradual weaning to a diet similar in fat, cholesterol, protein and carbohydrate content to rabbit milk maintained and enhanced the hypercholesterolemia. Reduction of the cholesterol content, and to some extent the fat content of this diet, decreased the plasma cholesterol level, but the type of dietary protein did not alter the results. After weaning, however, animals fed milk protein (casein) in the absence of dietary cholesterol became hypercholesterolemic, whereas those fed plant protein (soy protein isolate) remained normocholesterolemic.

Animal Population Groups

Noradrenergic influences on catalepsy.

Widespread depletion of forebrain noradrenaline, produced by the intracerebral injection of 4 microgram of 6-hydroxydopamine into the fibres of the dorsal noradrenergic bundle, potentiated the catalepsy induced by 20 mg/kg of morphine and severely attenuated the catalepsy induced by two separate cholinergic agonists, arecoline and pilocarpine. It did not, however, affect haloperidol catalepsy at any of the four doses tested. These results suggest that cholinergic catalepsy may be critically dependent on an intact noradrenergic substrate, perhaps through cholinergic receptors located either presynaptically on noradrenergic terminals or on the cell bodies of origin in the locus coeruleus. Noradrenaline appears to play a modulatory role in morphine catalepsy, although other sites of action must also be involved. Ascending noradrenergic systems do not appear to influence haloperidol catalepsy.

Animals

6-OHDA lesion to the dorsal noradrenergic bundle alters morphine-induced locomotor activity and catalepsy.

Rats show an initial depression in locomotor activity in response to doses of morphine greater than 5 mg/kg during the first hour after injection which is followed by a prolonged hyperactive phase. The effect of bilateral 6-hydroxydopamine (6-OHDA) lesions to the dorsal noradrenergic bundle on this biphasic action of morphine was studied. These lesions were found to significantly potentiate the locomotor depressant effects of morphine at 10.0 and 20.0 mg/kg while leaving the subsequent stimulant action of morphine unchanged. The cataleptic action of morphine at 20.0 mg/kg as measured in a separate test was also potentiated. These lesions were found to deplete hippocampal and cortical noradrenaline (NA) to 3% and hypothalamic NA to 32% of control values and also to cause significant increases in cerebellar and spinal NA. These data suggest a role for NA in the depressant effects of morphine but not in its subsequent stimulant actions which appear to be mediated by other neurochemical systems.

Animals

Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women.

The effect of dietary protein on the level of plasma cholesterol in young, healthy, normolipidemic women was investigated in two separate studies by feeding either a conventional diet containing mixed protein, or a plant protein diet in which the animal protein of the first diet was replaced by soy protein meat analogues and soy milk. The diets were similar with respect to carbohydrate, fat and sterol composition. The first study, lasting 73 days and involving six subjects, gave an indication that plasma cholesterol levels were lower on the plant protein diet. The second study, which incorporated a number of improvements based on experience, lasted 78 days and used a cross-over design involving two groups of five subjects each. In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet.

Adult

Serum lecithin-cholesterol acyltransferase activity in children with familial hyperbetalipoproteinaemia.

Serum (non-fasting) was obtained from 71 healthy school children (12-14 years) and from 16 children with the heterozygous form of familial hyperbetalipoproteinaemia being treated by diet or ion-exchange resin. The activity of lecithin-cholesterol acyltransferase (EC 2.3.1.43) expressed as nmol cholesterol esterified/hour/ml serum did not change with increasing concentrations of unesterified cholesterol in the healthy children. In children with familial hyperbetalipoproteinaemia, lecithin-cholesterol acyltransferase activity was higher than in the healthy children and this activity increased with increasing concentrations of unesterified cholesterol.

Acyltransferases

On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine.

The role of ascending noradrenergic (NA) and dopaminergic (DA) systems in intravenous self-administration of cocaine in rats was investigated by examining the effects of 6-hydroxydopamine-induced lesions of these systems on responding for the drug on a FR-1 schedule of reinforcement. Lesions of the dorsal and ventral NA bundles that reduced hippocampal-cortical NA by 96% and hypothalamic NA by 72% failed to have any effects on responding for cocaine. Lesions of the nucleus accumbens that reduced the DA content of this nucleus by 90% resulted in a significant and long-lasting (15 days) reduction in self-administration of cocaine. Apomorphine self-administration was not affected in the same animals. Identical lesions of the n accumbens had only transient (2-3 days) effects on food-reinforced operant responding, suggesting that the prolonged disruption of cocaine self-administration was not the result of motor deficits. The results are discussed with reference to the possibility that DA terminals in the n accumbens may mediate some of the positive reinforcing properties of cocaine.

Animals

Evidence for interactions between central noradrenergic neurons and adrenal hormones in learning and memory.

The role of ascending noradrenergic projections in the acquisition and retention of a passive avoidance step-down response was evaluated by means of bilateral stereotaxic 6-hydroxydopamine-induced lesions of these systems. Lesions of the dorsal NA bundle alone, or in combination with lesions of the ventral NA bundle, failed to influence either the acquisition or retention of the passive avoidance response. In contrast, animals subjected to dorsal and ventral NA bundle lesions and adrenalectomy exhibited severe deficits in both the acquisition and retention of this response, and this effect was of the same magnitude as was observed after posttrial injections of diethyldithiocarbamate (DDC, 300 mg/kg). Adrenalectomy by itself had a small but significant effect on retention but did not influence acquisition of the response. The results are discussed with reference to the possibility that interactions between adrenal hormones and central NA mechanisms may serve important roles in learning and memory. However, the data provide no support for the hypothesis that central NA neurons are, by themselves, critically involved in these phenomena.

Adrenalectomy

Chylomicron metabolism in rabbits fed diets with or without added cholesterol.

Intestinal lymph chylomicrons, isotopically labelled with radioactive triacylglycerol and cholesterol, were injected into normally fed and cholesterol-fed rabbits in order to establish the pattern of clearance of intestinal lipoproteins from the plasma. In normal rabbits the cholesterol moiety of chylomicrons was removed from the plasma less readily than triacylglycerol. In cholesterol-fed rabbits, the clearance of triacylglycerol was unaltered, but clearance of chylomicron cholesterol was further retarded. The majority of the injected lymph cholesterol was recovered in d less than 1.019 g/ml lipoproteins. These observations support the notions that clearance of chylomicron remnants is impaired in the rabbit, and that hypercholesterolaemia in the cholesterol-fed rabbit is due to an accumulation of chylomicron remnants in the plasma.

Animals