Biomedical subjects

T H Moran

Publications and source records attributed to T H Moran.

At least 127 records · Page 7Linked to original sources

PubMed1986

Mouse chimeras composed of trisomy 16 and normal (2N) cells: preliminary studies.

Many humans with trisomy 21 (Down Syndrome (DS)) have psychomotor and cognitive retardation, congenital heart disease, and hematologic abnormalities. Partial genetic homology exists between mouse chromosome 16 and human chromosome 21; thus, studies of the development of mice with trisomy 16 (Ts16) may provide important insights into the pathogenesis of these defects and into the mechanisms by which they arise in humans. Since Ts16 mice do not survive the late fetal period, chimeras have been formed between Ts16 and normal (2N) mouse embryos to rescue the Ts16 cells for postnatal studies. In this preliminary study of the postnatal development of such chimeras, we examined the proportion of Ts16 cells in a variety of tissues, including the coat, blood, placenta, heart, and brain. The Ts16 cells made significant contributions to almost all tissues examined. Aspects of the behavior and the neurochemistry of adult Ts16 less than-greater than 2N chimeras were found to differ significantly from control (2N less than-greater than 2N) chimeras and from animals of the two donor embryo strains. Ts16 cells comprised a substantial, but not predominant, proportion of cells in each brain region examined. Suggestions for definitive analyses are reviewed.

Animals↗

PubMed1986

The inhibition of feeding produced by direct intraintestinal infusion of glucose: is this satiety?

The food intake of two male rhesus monkeys (Macaca mulatta) trained to a daily four hour feeding period and prepared with intragastric and intraintestinal cannulas, was studied under three different experimental conditions intended to place glucose into the small intestine. In the first experiment, the monkeys drank 150 ml of 1 kcal/ml glucose which was then emptied from the stomach after 5 min. In this experiment, a mean of 21.6 kcal of glucose passed into the intestine. In the second experiment, 150 ml of 1 kcal/ml glucose was infused into the stomach, left for 5 min and again removed. In this experiment, a mean of 26.4 kcal of glucose passed the pylorus. In the third experiment, loads of glucose matching those passed through the pylorus on the first experiment were infused directly into the intestine. The feeding of the monkeys was monitored in 10 min intervals over a subsequent four hour meal period. While the glucose passed naturally from the stomach in the ingested or intragastric infusion situations did not affect feeding, glucose infused directly into the intestine significantly inhibited feeding throughout the first 60 min of the feeding period. These results suggest that some aspect of direct intraintestinal nutrient infusions produces an excessively powerful inhibitory signal on feeding.

Animals↗

PubMed1986

Cold water stress abolishes hyperactivity produced by cortical suction lesions without altering noradrenergic depletion.

The effect of forced cold water (15 degrees C) swimming on catecholamine depletions and behavioral hyperactivity produced by focal right hemispheric cortical suction lesions was assessed. Through the 30-day postoperative period, lesion and sham-operated control animals were placed in cold water for 5 min either four times at weekly intervals, once during the first postoperative week, or not at all. The effect of this cold water swim test was different for lesion and control animals. Stress at weekly intervals produced hyperactivity in control animals, but weekly stress in animals with focal suction lesions blocked the development of their expected hyperactivity. A single stress experience, 1 week postoperative, was also sufficient to block the development of hyperactivity in the lesion group. Stress, although affecting behavior, did not alter the pattern of norepinephrine depletions in animals receiving right hemispheric cortical suction lesions.

Animals↗

PubMed1986

Lateralized response to cortical injury in the rat: interhemispheric interaction.

This study was conducted to investigate the role of interhemispheric interaction in the production of spontaneous hyperactivity following right but not left frontal cortical suction lesions in the rat. Bilateral lesions, either simultaneous or left followed 1 week later by right, led to spontaneous hyperactivity and bilateral depletions of cortical norepinephrine concentrations. Rats given corpus callosum sectioning as neonates and frontal cortical suction lesions as adults developed spontaneous hyperactivity only when the right hemisphere was injured. These data suggest that lateralized spontaneous hyperactivity as elicited by small suction lesions of the right hemisphere does not depend on interhemispheric release or interaction and that at least the cortical mechanism is in the right hemisphere itself.

Animals↗

PubMed1986

Inhibition of gastric emptying and feeding by fenfluramine.

To assess the mechanism by which the anorectic agent fenfluramine influences feeding, we examined in Macaca mulatta the effect of intragastric fenfluramine (2 mg/kg) on both feeding and the gastric emptying of saline and glucose test meals. Gastric emptying was measured by the dye-dilution technique, using chronic indwelling intragastric cannulas. The emptying of normal saline was inhibited by fenfluramine as was the initial bolus phase of the emptying of glucose. In contrast, the subsequent controlled phase of glucose emptying was unaffected in two out of four animals, slightly inhibited in one, and strongly inhibited in only one monkey. Rhesus monkeys trained to drink a glucose solution to satiety drank, on average, 21% less after fenfluramine. The emptying of the consumed glucose solution from the stomach was reduced by 39%, whereas gastric volume at satiety was reduced by only 10%. The reduction of intake was strongly related to the degree of inhibition of gastric emptying. These results support an important role for the inhibition of gastric emptying in fenfluramine-induced suppression of feeding.

Animals↗

PubMed1986

The stomach, cholecystokinin, and satiety.

The stomach of the rhesus monkey empties liquids in a fashion that varies with the character of the solutions. Physiological saline empties exponentially. Glucose solutions empty biphasically--rapidly for the first minutes, then slowly and proportionately to glucose concentration to deliver glucose calories through the pylorus at a regulated rate (0.4 kcal/min). This prolonged and regulated second phase of gastric emptying depends on intestinal inhibition of the stomach. Cholecystokinin (CCK), a hormone released by food in the intestine, is an inhibitor of gastric emptying. In vitro receptor autoradiography demonstrates CCK receptors to be clustered on the circular muscle of the pylorus. Exogenous CCK, in doses that inhibit gastric emptying, will reduce food intake only if combined with an infusion of saline in the stomach. These observations indicate how gastric distension can be a means for provoking satiety. The variably sustained distension produced by the stomach's slow, calorically regulated emptying could prolong intermeal intervals and thus permit high-calorie meals to inhibit further caloric intake over time. CCK, by directly inhibiting gastric emptying during a meal, could promote gastric distension and so restrict the duration and size of individual meals.

Animals↗

PubMed1985

Asymmetrical effect of unilateral cortical lesions and amphetamine on DRL-20: a time-loss analysis.

Male Sprague Dawley rats received unilateral 1.5 mm diameter focal suction lesions of either the left or right orbito-frontal cortex and were tested for response to 6 doses of amphetamine sulfate ranging from 0.5 to 1.5 mg/kg on a DRL-20 schedule of reinforcement. Right hemispheric lesion animals obtained a greater number of control reinforcements and were more sensitive to amphetamine's disruptive effects, showing a greater dose-related decrease in water rewards obtained than left lesion animals. An analysis method is introduced which combines the interactive effects of premature responses and their IRT value in a way that relates directly to reinforcement attainment. Calculated total session time made unavailable for reinforcement due to premature responding, correlated negatively (r = -.942) with the number of reinforcements obtained.

Amphetamine↗

PubMed1984

Marked behavioral and biochemical sensitivity to lesion size in the posterior cortex of the rat.

Unilateral focal cortical suction lesions of varying diameter from 0.7 to 2.0 mm were made in the right posterior lateral cortex of rats. Only the 1.0 mm lesion size resulted in spontaneous postoperative hyperactivity. This increased activity was accompanied by significant elevations in substantia nigra and caudate nucleus dopamine concentrations. Other lesion sizes did not affect behavior or brain biochemical concentrations in this fashion. These results suggest a functional organization in this area of posterior cortex which affects both neurochemistry and behavior.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

Asymmetrical locomotor response to unilateral cortical injections of DSP-4.

The role of norepinephrine depletion in the lateralized production of spontaneous hyperactivity was assessed by unilateral fronto-cortical injections of either 10 or 20 micrograms of the noradrenergic neurotoxin, DSP-4 (N-2-chlorethyl-N-ethyl-bromobenzylamine hydrochloride). Ten micrograms of DSP-4 produced significant hyperkinesis only when injected into the right hemisphere. A 20 micrograms dose produced hyperactivity when injected into either hemisphere. DSP-4 injections resulted in significant NE and ipsilateral and contralateral 5HT depletions in the frontal cortex. The 20 micrograms right hemispheric injection significantly increased both DOPAC and DA levels in the contralateral caudate in a manner unrelated to behavior. These findings, in conjunction with results from previous neurotoxin studies, support a hypothesis of greater relative sensitivity to injury of right hemispheric NE terminal fields compared with injury to left hemispheric fields as demonstrated by spontaneous hyperactivity.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

Automated measurement of rearing behavior in adult and neonatal rats.

Three variables constituting an index of rearing behavior from an animal-activity monitoring system were compared with a standard visual rating at various ages of neonatal and adult rats. All three automated measures correlated significantly with measures rated by visual observation, although only the "number of vertical episodes" was similar in magnitude to the actual number of observed rearings. The height of the vertical sensors was critical in detecting rearings, although reliable results were obtained over a relatively wide range of heights. Analyses in neonatal rats demonstrated developmental progression in rearing behavior, with an onset around Day 15 of age. This automated technique was found to be useful and eliminated confounding variables, such as experimenter bias, commonly associated with visual observation techniques.

Age Factors↗

PubMed1984

Anatomic localization of cholecystokinin receptors to the pyloric sphincter.

In an effort to identify target sites within the gastrointestinal (GI) tract through which cholecystokinin (CCK) may exert its gastric inhibitory and satiety effects, the distribution of CCK receptors was mapped in the stomach and small bowel by in vitro radiography utilizing 125I-labeled Bolton-Hunter CCK-33. Specific receptor binding was localized to the circular smooth muscle layer of the pyloric sphincter. Negligible binding was observed in the oblique, circular, or longitudinal muscle layers of other GI levels. Moderate nonspecific binding was associated with mucosal tissue in all gastric sections. The restriction of CCK receptors to the circular smooth muscle of the pyloric sphincter suggests this location as the site through which CCK inhibits gastric emptying. Gastric distension secondary to this inhibition may be the mechanism for CCK-induced satiety.

Animals↗

PubMed1984

Asymmetrical effects of unilateral cortical suction lesions: behavioral characterization.

Behavioral effects of unilateral frontocortical suction lesions in the right and left hemisphere were characterized by a computerized activity monitoring system. Lesions of the right frontal cortex produced postoperative hyperactivity consisting of increases in the total distance traveled, average distance per movement, and average speed of movement. Vertical, rotational, and stereotypic measures were not changed. Animals receiving left hemisphere lesions did not differ from sham-operated controls on any behavioral variable. The lateralized hyperactivity resulting from lesions of the right frontal cortex was confined to increased length and speed of horizontal movement and did not appear to represent a generalized increase in all components of spontaneous activity.

Animals↗

PubMed1983

Stimulation-induced ingestion in neonatal rats.

Rat pups, 3, 6, 10 and 15 days old, received 500 ms pulse trains of electrical stimulation to the medial forebrain bundle (MFB) at the level of the lateral hypothalamus in the presence of milk. Pups receiving stimulation ingested more milk than littermate controls during a 30-min test at 3, 6 and 10 days of age. Day 15 pups did not. Stimulated pups through day 10 were more active than controls and exhibited the organized behaviors of mouthing, licking, gaping, stretch and even lordosis. Stimulated pups that ingested more milk continued to show increased activity through the 30-min test period, while the activity of control pups demonstrated a satiety effect. Milk augmented the activation of stimulation alone, increasing the incidence of all behaviors in 3-day-old pups and channelled the behavior of older pups into ingestion. Behaviors incompatible with ingestion such as lordosis were selectively inhibited by the presence of milk in stimulated day 10 pups. These results suggest a high degree of behavioral organization in neonatal rats than can be elicited by MFB stimulation and that becomes more goal-directed with age.

Animals↗

PubMed1983

A positioning fixture for L-shaped rotating undercutting microknives.

A simple, inexpensive device which controls the insertion, positioning and withdrawal of cortical undercutting microkinives is described. The device aids the "rolling" insertion of an L-shaped microknife which produces a minimum amount of overlying tissue damage while it holds the knife steady during undercutting and allows the blade to be withdrawn by way of the same track through which it was inserted.

Animals↗

PubMed1983

Organized behavioral responses to lateral hypothalamic electrical stimulation in infant rats.

Brief trains of electrical stimulation (500 msec) were administered to 3-, 6-, 10-, and 15-day-old rat pups through electrodes directed at the medical forebrain bundle (MFB) at the level of the lateral hypothalamus. Stimulation was given at three different frequencies: once per 30 sec, once per 20 sec, and once per 10 sec. Pups 10 days of age and younger became behaviorally activated by stimulation and reliably emitted a series of behavioral responses including mouthing, licking, pawing, gaping, probing, and stretch and lordosis responses. Behavior increased with increasing frequency of stimulation and became more organized with age. Sequences of organized behavior patterns are elicited by MFB stimulation which in their culmination take on the characteristics of motivational responses. Fifteen-day-old pups did not respond to these stimulation parameters. These findings indicate that the components of motivational systems are present and can be elicited at an early age. As development progresses, responses become more organized until stimulation parameters effective in rats 3 to 10 days of age become ineffective in activating behavior in day 15 pups.

Aging↗

PubMed1982

Cholecystokinin suppresses food intake by inhibiting gastric emptying.

In a search for the physiological mechanisms that could mediate and characterize a satiety function for the hormone cholecystokinin (CCK), we examined in Macaca mulatta the effect of intraperitoneal injections (0.1-0.8 microgram/kg) and intravenous infusions (60-240 ng.kg-1.h-1) of the C-terminal octapeptide of CCK on gastric emptying of saline test meals. Within these dose ranges, gastric emptying was inhibited by this hormone to a degree comparable with that produced by intraintestinal nutrient. The onset of the inhibition is rapid and its effect brief. At the doses of CCK that produce gastric inhibition, CCK would not affect feeding in a fasted monkey unless the stomach was filled with saline. This result suggests that a satiety influence of circulating CCK is an indirect one. The satiety effect depends upon inhibition of gastric emptying, which then leads to gastric distention with further food injection. CCK thus can be considered a link in a chain of physiological elements producing the short-term satiety that leads to the appropriate interruption of a meal or bout of feeding behavior.

Animals↗

PubMed1982

Postpyloric regulation of gastric emptying in rhesus monkeys.

Saline (0.9% NaCl) empties rapidly and exponentially from the stomach of the rhesus monkey, but glucose solutions empty at a calorie-constant rate of 0.4 kcal/min. By means of indwelling intragastric and intraduodenal cannulae we can demonstrate an inhibition on the delivery of saline from the stomach provoked by glucose placed beyond the pylorus. The inhibition varies directly with the glucose calories in the intestine and averages 2.5 min/kcal. That these two results (0.4 kcal/min and 2.5 min/kcal) are reciprocals suggests a feedback inhibition on the gastric emptying of nutrients arising from beyond the pylorus and adequate to explain the rate of glucose delivery to the intestine. A control theory description of gastric emptying that includes such feedback regulation can be derived from these data to explain the different gastric emptying patterns of nutrients and nonnutrient solutions. These patterns give this visceral system a precision in its management of nutrients that can provide information crucial to preabsorptive satiety.

Animals↗

PubMed1981

Intracranial self-stimulation in 3-day-old rat pups.

Three-day-old rat pups with electrodes directed at the medial forebrain bundle at the level of the lateral hypothalamic area were trained to push a paddle to receive electrical brain stimulation. Pups receiving stimulation that was contingent on lifting the paddle responded more frequently than did control pups and also learned a two-choice spatial discrimination task that was rewarded with brain stimulation. The experiments indicate that a neural substrate in the area of the medial forebrain bundle is involved in the central mediation of reinforcement in the rat pup.

Animals↗