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T H Moran

Publications and source records attributed to T H Moran.

At least 109 records · Page 6Linked to original sources
PubMed1988

Behavioral abnormalities induced by frontal cortical and nucleus accumbens lesions.

In previous studies, we have demonstrated that in male rats, unilateral right hemisphere lesions of either the frontolateral cortex or the nucleus accumbens (NAS) result in significant postoperative locomotor hyperactivity. In the present study we carried out two experiments to assess whether the production of hyperactivity in response to these two lesions is mediated through a common mechanism. In the first experiment, male Sprague-Dawley rats received either unilateral frontocortical suction and/or unilateral electrolytic lesions of the NAS. Only rats with lesions of the right hemisphere (suction and/or electrolytic) developed locomotor hyperactivity. Similar lesions in the left hemisphere did not result in behavioral changes. While both right cortical and NAS lesions alone produced hyperactivity, there was no additive effect of both lesions. In the second experiment, the effect of cortical lesions on NAS dopaminergic activity was assessed. Male Sprague-Dawley rats received either a right, left or sham frontocortical suction lesion, and were sacrificed 1, 2, and 4 weeks after surgery. Right hemisphere suction lesions produced a significant bilateral increase in NAS and caudate nucleus dopamine turnover (as measured by DOPAC/DA ratio) 4 weeks post-lesion, while similar left hemisphere lesions did not. These findings suggest that lesions in the dorsolateral frontal cortex and NAS may affect locomotor activity through a common mechanism mediated through the NAS.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Gastric control of food intake.

Inhibition of gastric emptying leads to enhanced satiety and this mechanism may contribute to the undereating observed after administration of cholecystokinin (CCK) and fenfluramine, and in patients with anorexia nervosa. Pyloric smooth muscle bears specific CCK receptors and the evidence suggests that a major site of action for CCK satiety is in the periphery. CCK receptors are widespread in the neonatal rat stomach but not in the brain and over the first two weeks of life binding in the stomach decreases and that in the brain increases. This and the finding that independent ingestion as well as gastric emptying are inhibited by CCK at birth suggest the stomach as its likely site of action in the neonatal rat. Fenfluramine inhibits feeding in animals and in patients with bulimia nervosa. In monkeys, fenfluramine inhibits gastric emptying and this action correlates with its feeding inhibition. Patients with anorexia nervosa who are acutely starving and rats maintained on a restricted diet have delayed gastric emptying. Anorexic patients showed abnormal reporting of both hunger and satiety, and, together with those with bulimia nervosa, often associated gastric contents with symptoms of eating disorder, indicating disturbed interpretation of gastric signals.

Animals↗
PubMed1988

A long-acting cholinesterase inhibitor reverses spatial memory deficits in mice.

The effects of the long-acting acetylcholinesterase (AChE) inhibitor, galanthamine, on spatial memory were investigated in mice. Mice received ibotenic acid or sham lesions to the nucleus basalis magnocellularis (nBM). Groups of nBM-lesioned and control mice were then trained on a modified Morris swim maze task. Each mouse was first placed on a platform and then into quadrants of the swim tank in a random order. Time required to find the hidden platform was measured. In different phases of testing, the animal had to find a platform that either remained in the same quadrant (reference memory component) or was moved daily (working memory component). The nBM-lesioned mice took significantly longer to find the platform as compared to controls on the working, but not on the reference, memory component of the task. Galanthamine (5.0 mg/kg, IP), given 3.5 hours before testing, improved performance on the working memory task in nBM-lesioned mice by 70% and strikingly impaired performance in controls. Galanthamine's ability to reverse cognitive deficits induced by nBM lesions and its comparatively long half-life suggest that it may be effective in treating the central cholinergic deficits in Alzheimer's disease patients.

Animals↗
PubMed1988

Cholecystokinin receptors on gallbladder muscle and pancreatic acinar cells: a comparative study.

To compare receptors for cholecystokinin (CCK) in pancreas and gallbladder, we measured binding of 125I-Bolton-Hunter-labeled CCK-8 (125I-BH-CCK-8) to tissue sections from guinea pig gallbladder and pancreas under identical conditions. In both tissues, binding had similar time-, temperature-, and pH dependence, was reversible, saturable and inhibited only by CCK related peptides or CCK receptor antagonists. Autoradiography localized 125I-BH-CCK-8 binding to the smooth muscle layer in the gallbladder. Binding of 125I-BH-CCK-8 to gallbladder sections was inhibited by various agonists with the following potencies (IC50):CCK-8 (0.4 nM) greater than des(SO3)CCK-8 (0.07 microM) greater than gastrin-17-I (1.7 +/- 0.3 microM) and by various receptor antagonists with the following potencies: L364,718 (1.5 nM) greater than CR 1409 (0.19 microM) greater than asperlicin = CBZ-CCK-(27-32)-NH2 (1 microM) greater than Bt2cGMP (120 microM). Similar potencies were found for the agonists and antagonists for pancreas sections. Inhibition of binding of 125I-BH-CCK-8 by 11 different analogues of proglumide gave similar potencies for both pancreas and gallbladder. The potencies of agonists in stimulating and antagonists in inhibiting CCK-stimulated contraction or amylase release correlated closely with their abilities to inhibit 125I-BH-CCK-8 binding to gallbladder or pancreas sections or acini, respectively. The present results demonstrate and characterize a method that can be used to compare the CCK receptors in guinea pig gallbladder and pancreas under identical conditions. Moreover, this study demonstrates that gallbladder and pancreatic CCK receptors have similar affinities for the various agonists and antagonists tested and, therefore, provides no evidence that they represent different subtypes of CCK receptors that can be distinguished pharmacologically.

Animals↗
PubMed1988

Gastric and nongastric mechanisms for satiety action of cholecystokinin.

The quantitative relationship between cholecystokinin's (CCK) inhibitory actions on gastric emptying and feeding was examined in rats. CCK (1, 2, 4, or 8 micrograms/kg) inhibited both the gastric emptying (determined by the dye dilution method) and ingestion of a 0.5-kcal/ml glucose solution in a 30-min testing period in 20-h deprived male Sprague-Dawley rats. Comparisons of the inhibitions of gastric emptying and feeding across the dose range of CCK revealed two components of CCK satiety: one defined by a linear relationship between the gastric inhibitory and feeding inhibitory actions of CCK through a dose range of 1-4 micrograms/kg, which accounted for 64% of the variability in the satiety action of CCK, and a second that appeared to be independent of the gastric inhibitory action of CCK.

Animals↗
PubMed1988

CCK-8 decreases food intake and gastric emptying after pylorectomy or pyloroplasty.

Specific binding sites for cholecystokinin (CCK) in the gastrointestinal tract of the adult rat are limited to the gastroduodenal region and are concentrated in the circular muscle of the pyloric sphincter. To determine the relationship of these pyloric muscle binding sites to the inhibition by CCK of food intake and of gastric emptying, these inhibitory effects of CCK were investigated in rats that had the pyloric sphincter surgically removed or that had the pyloric sphincter contractile mechanism damaged by a pyloroplasty procedure. CCK-8 decreased food intake and gastric emptying significantly in rats after pylorectomy or pyloroplasty. This demonstrates that an intact pyloric sphincter is not necessary for these inhibitory effects in rats. Because we found autoradiographic evidence for CCK receptors near the gastroduodenal anastomosis, however, the results suggest either that these receptors mediated the inhibition of food intake and emptying by CCK-8 or that these effects depend on CCK receptors in other locations.

Animals↗
PubMed1988

Cholecystokinin inhibits independent ingestion in neonatal rats.

The ability of the octapeptide of cholecystokinin (CCK-8) to inhibit independent ingestion was examined in 8-h deprived 1- to 10-day-old rat pups consuming milk from the surface of a test chamber. CCK significantly reduced the volume of milk ingested in 1-day-old rat pups at a dose of 100 ng/kg. The threshold effective dosage for inhibition of intake increased with age up to 10 days of age. The specificity of this suppression was evaluated in three ways. First, behavioral observation indicated that ingestive but not noningestive behaviors were suppressed by CCK. Second, desulfated CCK-8 was ineffective in suppressing milk ingestion. Finally, CCK inhibited milk intake stimulated by deprivation but did not affect dehydration-induced milk ingestion in 3-day-old rat pups. In addition to inhibiting intake, CCK inhibited the rate of gastric emptying of saline test meals in 1- and 3-day-old rat pups, and the threshold dosages for this suppression were identical to the thresholds for the inhibition of ingestion. These results indicate that the gastrointestinal peptide CCK is both behaviorally and physiologically active in newborn rat pups and support a role for gastric inhibition in the satiety action of CCK.

Animals↗
PubMed1988

Pylorectomy reduces the satiety action of cholecystokinin.

Rat gastric cholecystokinin (CCK) receptors are localized to the circular muscle layer of the pyloric sphincter, and a role for these receptors in the mediation of CCK satiety has been proposed. To directly assess the contribution of this receptor population in CCK satiety, the area of the pyloric sphincter containing these receptors was surgically removed, and the behavioral responses to CCK were compared pre- and postpylorectomy. The presence of CCK receptors in the gastroduodenal junction was assessed by either in vitro CCK receptor autoradiography or in vitro contractile response to CCK. The results depended on the time after pylorectomy during which testing occurred. Two to 3 wk after pylorectomy rats demonstrated a significant attenuation of CCK satiety such that while the response to 1 and 2 micrograms/kg was intact, any additional inhibition by 4 and 8 micrograms/kg was eliminated. At this time, no evidence of CCK receptors around the gastroduodenal junction was found. In contrast, 2-3 mo after pylorectomy, the normal dose-response inhibition to CCK was intact. Evidence for the presence of CCK binding sites at the gastroduodenal junction was found by both autoradiography and physiological assessment. These results indicate a role for pyloric CCK receptors in the mediation of CCK satiety.

Animals↗
PubMed1988

Lateralized effect of cerebral infarction on spinal fluid monoamine metabolite concentrations in rats.

Using a rat model of stroke, we studied the effect of unilateral middle cerebral artery ligation on cerebrospinal fluid monoamine metabolites at different intervals over a 40-day postoperative period. Male Sprague-Dawley rats were divided into four groups: an unoperated control group (n = 9), a sham-operated group (n = 9), a right middle cerebral artery ligation group (n = 10), and a left middle cerebral artery ligation group (n = 10). One hundred microliters of cerebrospinal fluid were collected percutaneously from the cerebellomedullary cistern just before and 5, 20, and 40 days after the surgical procedure. Monoamine metabolites--3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxy-indoleacetic acid (5-HIAA), and homovanillic acid (HVA)--were measured using high-performance liquid chromatography. MHPG concentration in the right lesion group was significantly depleted from control levels 5, 20, and 40 days after surgery. No such depletion was observed in the left lesion rats. Concentration of 5-HIAA was relatively lower at Days 5 and 20 in the right lesion group than in the left lesion group. HVA concentration did not differ among the groups at any time. Our study has demonstrated a differential effect of unilateral ischemia on cerebrospinal fluid neurochemistry in rats dependent on the cerebral hemisphere involved.

Analysis of Variance↗
PubMed1987

Transport of cholecystokinin (CCK) binding sites in subdiaphragmatic vagal branches.

In order to evaluate vagal cholecystokinin (CCK) binding sites as potential target sites for the satiety actions of CCK, their presence, axonal flow and pharmacological specificity in subdiaphragmatic vagal branches were examined by autoradiography utilizing 125I-Bolton Hunter CCK-33. Specific CCK binding and axonal transport were found in vagal trunks and all abdominal vagal branches. Binding was inhibited by unlabelled CCK-8, but not by desulfated CCK-8. The pharmacological specificity and transport of CCK binding sites to subdiaphragmatic branches indicate a potential role in mediating CCK's satiety effect.

Animals↗
PubMed1987

Differential and asymmetrical behavioral effects of electrolytic or 6-hydroxydopamine lesions in the nucleus accumbens.

Sprague-Dawley rats received either unilateral or bilateral electrolytic or 6-hydroxydopamine (6-OHDA) lesions in the nucleus accumbens (n. acc.) and daily spontaneous activity was measured in home cage running wheels for 30 days postoperatively. Bilateral electrolytic lesions increased activity to 230% of preoperative baseline. Right electrolytic lesions produced a 50% increase in activity while left lesion rats were not significantly different from sham-operated controls. Conversely, 6-OHDA lesions depressed activity. Bilateral 6-OHDA lesions had the greatest depressant effect upon activity while unilateral left or right n. acc. treatments produced relatively less hypoactivity. Results support an asymmetrically organized serial inhibition model of spontaneous locomotor control.

Animals↗
PubMed1987

The development of daytime rearing behavior in methylazoxymethanol-treated rats: methodological considerations.

The development of daytime rearing behavior was studied in the offspring of pregnant rats which received injections of methylaxymethanol acetate (MAM) or saline during the 15th day of gestation. MAM and control rats were tested at 10, 15, 20, 25, and 30 days of age. The results indicated that the onset of rearing for both groups appeared at approximately 15 days of age, with no significant differences found between sexes. No rearing deficits were seen in MAM rats through 25 days of age despite the fact that these animals sustained greater than a 50% reduction in telencephalic mass. However, at 30 days of age MAM rats reared for significantly longer periods of time during each episode than did their control counterparts, although the actual number of rears did not differ between groups. The results are discussed in terms of neuroplastic events which follow MAM-induced damage and the need for multivariate research when analyzing rearing behavior.

Animals↗
PubMed1987

Development of cholecystokinin binding sites in rat upper gastrointestinal tract.

Autoradiography using 125I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat.

Age Factors↗
PubMed1986

Anatomical predictors of behavioral recovery following fetal striatal transplants.

The ability of fetal striatal transplants to reverse behavioral deficits produced by kainic acid striatal lesions was assessed in adult female rats. Three groups of animals, including a lesion-only, a lesion and transplant, and a control group were assessed on several measures, including rewarded alternation, a sensorimotor neurological examination and on spontaneous locomotor activity. Anterior-medial striatal lesions led to a decreased performance on the rewarded alternation and sensorimotor neurological examination and caused the animals to be hyperactive in horizontal and stereotypical movements. The transplants partially reversed the rewarded alternation and locomotor deficits, but had little effect on the sensorimotor neurological deficit. Histologically, the transplanted fetal tissue survived well within the kainate-treated striatal region, and partially reversed the lesion-induced cell loss. Neuronal cell counts successfully predicted outcome on several of the behavioral measures, suggesting that the extent of behavioral recovery depends partially on quantitative aspects of the transplantation methodology.

Animals↗
PubMed1986

Behavioral recovery following kainic acid lesions and fetal implants of the striatum occurs independent of dopaminergic mechanisms.

Transplantation of fetal striatal tissue into rats with kainic acid lesions of the striatum reversed the spontaneous locomotor abnormalities caused by the lesions, but had no effect on the lesion-induced hyperactivity that followed amphetamine or apomorphine injection. Conversely, transplants into intact (non-lesioned) striatum led to abnormalities in spontaneous locomotion, but did not effect locomotion under amphetamine or apomorphine conditions. Dopamine autoradiography found a relative absence of dopamine receptors within the transplants. These results suggest that the mechanism which accounts for transplant-induced recovery of spontaneous locomotion is independent of striatal dopamine mechanisms.

Animals↗
PubMed1986

Two brain cholecystokinin receptors: implications for behavioral actions.

The distribution and relative specificity of cholecystokinin (CCK) receptors in the rat brain was mapped by in vitro autoradiography with [125I]CCK-33. We identified two distinct binding patterns, suggesting two CCK receptor types. The first is widespread and relatively non-specific. The second, localized to a few subcortical nuclei, has the specificity demonstrated for pancreatic CCK receptors. Localization of this receptor type to the area postrema provides a possible entry site into brain for circulating CCK that would distinguish between CCK and gastrin and could mediate some of CCK's behavioral effects.

Animals↗
PubMed1986

Methylazoxymethanol acetate cortical hypoplasia alters the pattern of stimulation-induced behavior in neonatal rats.

In an attempt to identify a neural basis for the developmental progression in the organization of behavior evidenced in responses to lateral hypothalamic electrical stimulation, the responses to medial forebrain bundle (MFB) stimulation of pups whose mothers had been treated with saline or the antimitotic agent methylazoxymethanol acetate (MAM) on gestational Day 15 were measured. Administration of MAM at this age produces a severe and lasting cortical hypoplasia. Monopolar stainless-steel electrodes aimed at the MFB at the level of the lateral hypothalamus were implanted in pups 3, 10, 15 and 20 days of age and responses to 500 ms trains of stimulation were recorded. At 3 and 10 days of age, the number of behavioral responses increased with increasing frequency of stimulation in both MAM and saline-treated pups. Ten-day-old MAM-treated pups, however, displayed 'significantly less behavioral organization in their pattern of responding to stimulation. MAM pups, unlike saline-treated pups, continued to respond to stimulation at Day 15. Even at postnatal Day 20 some MAM-treated pups responded to stimulation. Neurochemical analysis of the brains of littermates demonstrated a significant increase in choline acetyltransferase levels indicating a relative hyperinnervation of afferent cholinergic terminals, confirming the cortical hypoplasia and replicating earlier work. These results suggest a role for the developing neocortex in organizing the behavioral responses to stimulation. The onset of cortical inhibitory mechanisms may channel behavioral responses in normally developing pups and prevent the characteristic activational responses to stimulation in Day-15 pups.

Animals↗