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Biomedical subjects

T H Moran

Publications and source records attributed to T H Moran.

At least 91 records · Page 5Linked to original sources
PubMed1991

Time course of effects of preloads high in fat or carbohydrate on food intake and hunger ratings in humans.

A high-carbohydrate (CHO) yogurt (81% CHO) and a high-fat yogurt (65% fat), containing similar levels of protein, were given in equal volumes as preloads to 14 normal-weight, nondieting males and 14 normal-weight, nondieting females. The yogurts were formulated to have similar energy densities and sensory properties, so that differences in responses to the preloads would depend on postingestive physiological effects. Three intervals (30, 90, and 180 min) between the preloads and a self-selection meal consisting of a variety of foods were utilized. The self-selection meal was served at the subject's normal lunchtime under all conditions. In the 30-min-delay condition, subjects accurately compensated for the calories in the preloads compared with a no-preload condition, but as the interval increased, compensation was less precise. No significant differences in subsequent food intake were found between the high-CHO and high-fat yogurts at any time interval. Also, there were no differences in ratings of hunger and fullness between the yogurts. The macronutrient composition of the preloads did not affect the types of foods, or macronutrients, consumed at lunch.

Adult↗
PubMed1991

Integration of vagal afferent responses to gastric loads and cholecystokinin in rats.

The neurophysiological responses to 2-ml intragastric saline loads and 100-pmol celiac artery infusions of cholecystokinin (CCK) were obtained from 20 vagal afferent fibers in 14 rats. Two groups of fibers were identified. Discharge rates of group I fibers (n = 16) were significantly increased by gastric loading, adapted slowly to maintained gastric volume, and were inhibited by load withdrawal. CCK elicited a significant increase in the discharge rate of these group I fibers. Prior exposure to CCK nearly doubled the response of these fibers to a subsequent gastric load. In contrast, group II fibers (n = 4) increased firing rate only during infusion of a gastric load and showed rapid adaptation and no response to CCK. CCK failed to alter subsequent responses to gastric loads in these fibers. These results 1) demonstrate an integration of signals elicited by exogenous CCK and gastric loads at the level of vagal afferent fibers and 2) imply that aspects of CCK's inhibition of food intake may derive from CCK's ability to mimic and amplify vagal afferent activity provoked by meal-related gastric events.

Afferent Pathways↗
PubMed1991

Effects of pylorectomy on cholecystokinin-induced inhibition of liquid gastric emptying.

The present study was designed to investigate a role for the pyloric sphincter and its population of cholecystokinin (CCK) receptors localized to the circular muscle layer in the inhibition of gastric emptying produced by exogenously administered CCK in rats. We examined the ability of two doses of CCK to inhibit the gastric emptying of 10-ml saline (0.9% NaCl) and glucose (0.125 g/ml) test meals in rats equipped with chronic gastric fistulas before and after surgical removal of the region of the pylorus containing CCK receptors. Preoperatively, CCK (2 and 8 micrograms/kg) inhibited gastric emptying of both saline and glucose. Pylorectomy did not significantly alter the baseline saline and glucose emptying and did not alter the ability of CCK to inhibit the emptying of the saline test meals. In contrast, pylorectomy eliminated the ability of CCK to inhibit glucose emptying. These results demonstrate that the inhibition of gastric emptying by CCK may involve multiple mechanisms depending on the character of the gastrointestinal contents.

Animals↗
PubMed1991

Gastric loads potentiate inhibition of food intake produced by a cholecystokinin analogue.

We have proposed that cholecystokinin's (CCK) inhibition of gastric emptying contributes to its ability to inhibit food intake. To directly test this hypothesis in rats, the effect of the presence of a 5-ml gastric saline load on the ability of a long-acting cholecystokinin analogue U-67827E (0.1-10.0 nmol/kg) to inhibit intake of a 0.5 kcal/ml glucose solution was measured. The CCK analogue alone inhibited intake at a threshold dose of 2.5 nmol/kg. Although lower doses of the CCK analogue alone had no effect on subsequent glucose intake, when combined with the gastric load such doses did significantly inhibit intake. Thus the presence of a gastric load reduced the threshold dose of the CCK analogue required to inhibit intake. Furthermore, at suprathreshold doses, the peptide-load combination suppressed intake more than the peptide alone. In addition, administration of 0.5 and 5.0 nmol/kg doses of the CCK analogue inhibited gastric emptying at 10, 20, and 30 min in a dose-dependent fashion. The CCK analogue's inhibition of food intake and gastric emptying were reversed by pretreatment with 100 micrograms/kg L364,718, indicating that the analogue was having its effects by interacting with specific type A CCK receptors. Together these data support the notion that CCK satiety derives from an integration of the visceral afferent signals generated by CCK's promotion of gastric distension and those produced directly by CCK.

Analysis of Variance↗
PubMed1990

Receptor heterogeneity for bombesin-like peptides in the rat central nervous system.

As an initial characterization of bombesin binding sites in the rat central nervous system, we examined the pharmacological specificity of binding of bombesin (BBS) and several BBS analogs to rat cortex and compared these results to those for rat pancreas. In addition, we used in vitro receptor autoradiography to evaluate binding of 125I-[Tyr4]bombesin and 125I-Bolton-Hunter neuromedin B (NMB) to several regions of the rat brain. The results of the pharmacological study indicated that the pancreas and cortex had different binding affinities for BBS-like peptides. While cortical binding sites had a high affinity for NMB, pancreatic binding sites had almost no affinity for NMB. Results from the autoradiographic study demonstrated that BBS receptor heterogeneity exists in individual nuclei in the rat brain. Some nuclei have a high affinity for NMB, similar to cortical BBS binding sites, other regions have a low affinity similar to pancreatic BBS binding sites. These results provide evidence that subtypes of BBS receptors are present in different tissues and within discrete regions of the rat central nervous system.

Animals↗
PubMed1990

Hemispheric asymmetry in behavioral response to D1 and D2 receptor agonists in the nucleus accumbens.

The present study examined the locomotor response of rats to unilateral injections of the mixed D1/D2 agonist apomorphine, the D2 agonist quinpirole, and the D1 agonist SKF 38393 into the left or right nucleus accumbens (NA) of male Sprague-Dawley rats. There were 2 main findings. First, unilateral (left or right) injections of apomorphine, quinpirole, or SKF 38393 all provoked locomotor hyperactivity. The second and more important finding was that, at specific dosages, apomorphine and SKF 38393 injections into the right NA produced significantly more locomotor hyperactivity than identical injections into the left NA. These findings suggest the presence of asymmetries in the NA which may involve quantitative differences in the distribution of D1 and D2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Central and peripheral vagal transport of cholecystokinin binding sites occurs in afferent fibers.

The effects of various vagal lesions on cholecystokinin (CCK) binding sites in the nucleus tractus solitarii (NTS) and area postrema (AP) and the peripheral transport of CCK binding sites in the cervical vagus were examined in rats by in vitro autoradiography with [125I]CCK-8. Unilateral supraganglionic, but not subdiaphragmatic vagotomy significantly reduced CCK binding in the ipsilateral NTS. Specific unilateral afferent, but not efferent, vagal rootlet transections also significantly reduced NTS CCK binding ipsilateral to the transections. None of the vagal lesions altered CCK binding in the AP. Infraganglionic but not supraganglionic vagotomy eliminated the peripheral transport of vagal CCK binding sites. Together these results demonstrate that CCK receptors in the NTS are located on vagal afferent terminals, that CCK receptors in the AP are likely postsynaptic to a vagal afferent input and that the peripheral and central transport of vagal CCK binding sites occurs in afferent fibers.

Afferent Pathways↗
PubMed1990

Remote lateralized changes in cortical [3H]spiperone binding following focal frontal cortex lesions in the rat.

Positron emission tomography (PET) studies in stroke patients have shown that right hemisphere lesions lead to increases in ipsilateral (compared to contralateral) cortical S2-serotonin receptors, while left hemisphere lesions do not. To assess whether similar lateralized changes in cortical S2-receptors could be demonstrated in response to brain injury in the rat, [3H]spiperone (SP) autoradiography was performed 30 days after unilateral cortical suction lesions. Right lesions produced bilateral increases in total SP binding in frontal cortex (excluding the lesion site): 48% greater than after left lesions, and 23% greater than shams. Left lesions led to bilateral decreases in S2-receptors in the frontal and perirhinal cortex and these decreases were asymmetric. There was a greater decrease in the hemisphere contralateral to the lesion than in the side with the lesion. Frontal S2-receptor binding was positively correlated with running wheel activity in all animals with lesions, regardless of lesion side. These results suggest that there is a lateralized receptor and behavioral response to focal injury in rats, analogous to that previously observed in humans.

Animals↗
PubMed1990

Caloric compensation for lunches varying in fat and carbohydrate content by humans in a residential laboratory.

Two groups of three subjects participated in a residential study that assessed the effects of varying the macronutrient and caloric content of a required lunch meal on subsequent food choice and intake. Lunches contained 431 or 844 kcal, with the caloric differential created by manipulating the calories derived from either fat or carbohydrate (CHO). Each lunch condition (high-fat, high-CHO, low-fat, and low-CHO) was examined for 3 consecutive days. Subjects controlled their own patterns of food intake and could consume any item or number of items at any time during the day or night. There were no significant differences in total daily caloric intake across conditions, indicating that subjects compensated for the caloric content of the lunch regardless of the macronutrient content. Total daily caloric intake under the high-fat and high-CHO conditions was 2824 +/- 151 (mean +/- SEM) and 2988 +/- 187 kcal, respectively, whereas intake under the low-fat and low-CHO conditions was 2700 +/- 131 and 2890 +/- 247 kcal, respectively.

Adult↗
PubMed1990

Characterization of cholecystokinin receptors on the sphincter of Oddi.

To characterize directly the ability of cholecystokinin (CCK) to interact with receptors on the sphincter of Oddi (SO), we measured binding of 125I-labeled Bolton-Hunter-labeled COOH-terminal octapeptide of cholecystokinin (125I-BH-CCK-8) to tissue sections from the guinea pig SO. Autoradiography localized binding of 125I-BH-CCK-8 over the SO smooth muscle layer. Binding was saturable, specific, dependent on time, pH, and temperature, and was reversible. Binding of 125I-BH-CCK-8 was inhibited by various CCK receptor agonists with the following potencies: CCK-8 much greater than des(SO3)CCK-8 much greater than gastrin-17-I and by various CCK receptor antagonists with the following potencies: L-364,718 greater than proglumide analogue 10 much greater than carbobenzoxy-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-NH2 greater than N2,O2' dibutyryl guanosine 3',5'-cyclic monophosphate. The potencies of agonists in stimulating and of antagonists in inhibiting CCK-8-stimulated SO contractions correlated closely with their abilities to inhibit binding of 125I-BH-CCK-8. Analysis of binding of 125I-BH-CCK-8 to SO tissue sections revealed two classes of CCK binding sites: a high-affinity site [dissociation constant (Kd) 0.2 nM] and a low-affinity site (Kd 70 nM). Atropine or tetrodotoxin (TTX) caused a similar rightward shift of the CCK-8 dose-response curve for stimulation of SO contraction. Comparison of receptor occupation to CCK-8-induced contraction suggested that CCK-8 occupation of the high-affinity binding site correlated with contraction in the absence of atropine and the low-affinity CCK binding with contraction in the presence of atropine or TTX.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Hyperactivity following posterior cortical injury is lateralized, sensitive to lesion size and independent of the nigrostriatal dopamine system.

In a previous study, we reported that a specific size cortical suction lesion of the right posterior cortex in rats produced hyperactivity and increased concentrations of dopamine in the nigrostriatal pathway. The present study extended those findings by addressing whether this phenomenon is lateralized to the right posterior cortex and whether the increases in nigrostriatal dopamine are necessary for the behavioral changes produced by the lesion. Right posterior cortical lesions of 1.8 mm diameter produced spontaneous hyperactivity over a 30-day postoperative period while identically placed 1.3 mm or 2.4 mm diameter lesions did not. Left hemisphere lesions of 1.3 mm, 1.8 mm or 2.4 mm diameter also failed to produce hyperactivity. The hyperactivity response to 1.8 mm diameter lesions of the right posterior cortex was not blocked by 70% depletions in nigrostriatal dopamine produced by bilateral nigral injections of 6-hydroxydopamine two weeks prior to cortical lesions. These findings suggest that hyperactivity following right posterior cortical lesions is lateralized and is not dependent upon changes in the nigrostriatal dopaminergic pathway.

Animals↗
PubMed1989

The use of fetal neocortical transplants to treat the hyperactivity resulting from cortical suction lesions in adult rats.

Focal suction lesions of the right frontoparietal cortex in rats produce locomotor hyperactivity. We attempted to reverse these changes by grafting homologous cortex from 16-day-old embryos into the lesion site. Various aspects of activity were measured in computerized photocell chambers until 14 weeks past transplantation. Three groups of animals were tested: sham-operated controls, lesions only (LO), and lesion plus transplant (LT). Hyperactivity was demonstrated for all measures in LO and/or LT groups. There was a partial reversal by the transplants of the increases in vertical activity produced by lesions at 14 weeks after transplant. However, on other measures, such as distance per movement, only LT animals were ever hyperactive, and on others, such as total distance, hyperactivity appeared earlier in the LT group than in LO. Brain chemistry analyses revealed right-sided norepinephrine depletions in posterior cortex in all groups and a bilateral cortical serotonin depletion in LT animals only. Results suggest that transplanted tissue can either ameliorate or exacerbate locomotor changes produced by cortical ablation depending on the particular behavior and on when it is measured.

Animals↗
PubMed1989

Developmental and hormonal factors in the sexually dimorphic, asymmetrical response to focal cortical lesions.

The developmental and hormonal determinants of the lateralized response to focal cortical suction lesions were examined in a series of experiments. In an initial study, Sprague-Dawley male rats 25, 30, 55 or 90 days of age, received right unilateral focal frontocortical suction lesions. Only 90-day-old rats developed hyperactivity, suggesting a specific role for maturational factors in the production of this response. Prepubertally castrated adult male rats receiving right frontocortical suction lesions at 90 days also failed to develop hyperactivity, suggesting that sexual maturational factors and/or the presence of testosterone are necessary for the expression of this response. Testosterone implants, producing physiological relevant levels of circulating testosterone reinstated the hyperactivity response to adult cortical lesions in prepubertally castrated male rats. Similar lesions in the left hemisphere, however, did not produce hyperactivity in castrated male rats with testosterone replacement. Finally, in ovariectomized adult female rats, testosterone did not allow the expression of a hyperactivity response to right frontocortical suction lesions. Together, these results demonstrate both an organizational and permissive role for sex steroids in the sexually dimorphic asymmetrical response to cortical injury.

Aging↗
PubMed1989

Food intake in baboons: effects of a long-acting cholecystokinin analog.

Food intake of four adult male baboons (Papio c. anubis) was monitored during daily experimental sessions lasting 22h. Food was available under a two-component operant schedule. Following completion of the first "procurement component" response requirement, access to food, i.e. a meal, became available under the second "consumption component" during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. A long-acting cholecystokinin (CCK) analog U-67827E (U-67: 0.80-3.2 micrograms/kg) was administered, in the thigh muscle, at 1100 hrs immediately prior to the start of the daily session on Tuesdays and Fridays. U-67 significantly reduced intake during the first 8-h of the session, and intake during the entire 22-h session. The decreased intake was due to a significant decrease in the size of the first meal of the session as a consequence of decreased duration of feeding without a change in response rate. U-67 also produced dose-dependent increases in latency to the first meal of up to 2.5 h. These results demonstrate that a long-acting CCK analog decreases food intake over a prolonged period of time in a naturalistic feeding situation. In addition, the effects of U-67 were limited to the consumption component, suggesting that this CCK analog affected food intake by interacting with physiological mechanisms specifically associated with feeding.

Animals↗
PubMed1989

Bombesin affects feeding independent of a gastric mechanism or site of action.

Peripherally administered bombesin has been demonstrated to inhibit food intake in a variety of species. Although the behavioral actions of bombesin are well characterized, neither the site of action nor mechanism through which bombesin affects feeding has been demonstrated. To test the hypothesis that bombesin's feeding effects are through a gastric inhibitory mechanism or a gastric site of action we examined the potential relationship between the inhibition of gastric emptying and the inhibition of intake produced across a dose range of bombesin and compared the relative potency of bombesin analogues for inhibiting feeding with their affinity for gastric bombesin receptors. Comparisons of the inhibitions of gastric emptying and feeding produced by 2, 4, 8, or 16 micrograms/kg of bombesin revealed no relationship, and, in fact, no gastric inhibitory action was evident. The feeding inhibitory actions of dose ranges (100 pmol-100 nmol) of litorin, ranatensin, acetylated gastrin-releasing peptide-(20-27) [AcGRP-(20-27)] and bombesin-(8-14) fragment were assessed and compared with bombesin. These compounds inhibited feeding with a relative potency of bombesin greater than AcGRP-(20-27) greater than ranatensin greater than litorin greater than bombesin-(8-14). This rank order of potency differed from the relative affinity of these compounds for gastric bombesin receptors for which all of these compounds except bombesin-(8-14) have a greater affinity than does bombesin. The results of these two experiments suggest that bombesin's satiety actions are not mediated by a gastric inhibitory mechanism or through a gastric site of action.

Animals↗
PubMed1988

Receptor characteristics and recovery of function following kainic acid lesions and fetal transplants of the striatum. I. Cholinergic systems.

The relationship between striatal muscarinic cholinergic receptor development and locomotor activity/T-maze alternation behavior in adult female rats with kainic acid lesions (kal) and fetal transplants of the striatum (str) was examined. Kal led to a number of deficits under conditions of spontaneous locomotion, including: (1) decreased stereotypical and increased horizontal movements during spontaneous overnight locomotion, (2) decreased spontaneous alternation on a T-maze, and (3) deficits on a sensorimotor neurological exam. Lesion-induced deficits following injection with cholinergic agonists (pilocarpine)/antagonists (scopolamine) included: (1) hypoactivity on vertical activity and stereotypical activity following scopolamine injection, and (2) increased stereotypical activity and decreased horizontal activity following pilocarpine injection. Transplants differentially affected the different types of behavioral deficits. Transplants reversed some of the deficits under conditions of spontaneous locomotion, including the hyperactivity noted during the night period, but only partially reversed the sensorimotor neurological exam and had no effect on spontaneous alternations in the T-maze. The transplants did not reverse the lesion-induced deficits following scopolamine injection, but partially reversed the lesion-induced changes in locomotion following pilocarpine injection. The striatal transplants had reduced numbers of M1 but increased numbers of M2 muscarinic cholinergic receptors. Cholinergic receptor density correlated with scores on the sensorimotor functioning and alternation tasks, but not with the locomotor measures. Conversely, the cross-sectional area of the str correlated strongly with the transplant-induced recovery in the lesion group. These results suggest that the development of cholinergic receptor systems within the transplants proceeds abnormally, and that the abnormal development of the transplant may impact on the transplant's ability to remediate lesion-induced deficits.

Animals↗
PubMed1988

Receptor characteristics and recovery of function following kainic acid lesions and fetal transplants of the striatum. II. Dopaminergic systems.

This experiment reports the development of striosomal-like patches in fetal striatal transplants grafted either into the intact, or kainic acid-lesioned, striatum of adult female rat brain. Although D2 receptor density approached control levels in the area of the patches, otherwise the transplanted striatum was relatively empty of dopamine receptors, and overall D2 development of the graft was strikingly reduced from controls. Transplants reversed lesion-induced hyperactivity under saline, but not amphetamine/apomorphine conditions, and led to an increased sensitivity of lesion and grafted animals following haloperidol injection. Transplants into the intact brain led to a lesion-like effect. M1 muscarinic cholinergic/D2 receptor density inversely correlated with behavior following amphetamine/apomorphine injections, while striatal cross-sectional area inversely correlated with activity after saline injection. These results suggest that abnormal maturation of the grafted striatum correlates with deficits in activity in grafted animals, and suggests that abnormal transplant development significantly impacts on transplant-induced behavioral changes.

Amphetamines↗