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A C Scallet

Publications and source records attributed to A C Scallet.

69 records · Page 4Linked to original sources
PubMed1988

Neuropathological evaluation by combined immunohistochemistry and degeneration-specific methods: application to methylenedioxymethamphetamine.

To best interpret the significance of neurological alterations produced by chemicals, the changes in morphological as well as neurochemical parameters must be measured and compared to each other. We have devised an approach to readily label microscopic sections for multiple antigens (neurotransmitters, enzymes, peptides, etc.) as well as for the demonstration of degenerating structures by silver impregnation. Here, we applied silver-staining together with immunolabelling of 5-HT and tyrosine hydroxylase (the rate-limiting enzyme for dopamine synthesis) to study neurohistological alterations produced by methylenedioxymethamphetamine (MDMA), a hallucinogenic stimulant previously used as an adjunct to psychotherapy and now a popular recreational drug ("Ecstasy"). Single oral doses of 40 or 80 mg/kg MDMA doubled the density of silver-impregnated (degenerating) fiber terminals in the caudate nucleus compared to controls, when rats were sacrificed 18 hours after treatment. Four months after two 40 mg/kg oral doses per day for four days, rats had a reduced neurochemical content of 5-HT in the hippocampus, and fewer immunostainable 5-HT axons per unit area in the hippocampal stratum lacunosum but no change in brain-stem neurochemical 5-HT content or in the numeric density of 5-HT-positive cell bodies in the dorsal raphe nucleus. The neurohistology suggests interpreting the changes in neurochemical content of serotonin produced by MDMA as due to degeneration followed by subsequent loss of 5-HT axons, rather than a decrease in the rate of neuronal 5-HT synthesis or a toxicity directed toward 5-HT cell bodies. The combination of neurohistological and neurochemical evaluation will continue to prove useful in comprehensive evaluation of the neurological effects of chemical exposure.

3,4-Methylenedioxyamphetamine↗
PubMed1987

Morphometric studies of the rat hippocampus following chronic delta-9-tetrahydrocannabinol (THC).

Persistent behavioral effects resembling those of hippocampal brain lesions have been reported following chronic administration of marijuana or its major psychoactive constituent, delta-9-tetrahydrocannabinol (THC) to rats. We used morphometric techniques to investigate the effects of chronic THC on the anatomical integrity of the hippocampus. Rats dosed orally for 90 days with 10 to 60 mg/kg THC or vehicle were evaluated by light and electron microscopy up to 7 months after their last dose of drug. Electron micrographs revealed a striking ultrastructural appearance and statistically significant decreases in mean volume of neurons and their nuclei sampled from the hippocampal CA3 region of rats treated with the highest doses of THC. A 44% reduction in the number of synapses per unit volume was demonstrated in these same rats. Golgi impregnation studies of additional groups of rats treated with 10 or 20 mg/kg/day THC and sacrificed 2 months after their last treatment with THC revealed a reduction in the dendritic length of CA3 pyramidal neurons, despite normal appearing ultrastructure and no changes in synaptic density. The hippocampal changes reported here may constitute a morphological basis for behavioral effects after chronic exposure to marijuana.

Administration, Oral↗
PubMed1987

Hypothalamic neurotoxins alter the content of immunoreactive cholecystokinin in pituitary.

Monosodium glutamate and bipiperidyl mustard both produce mediobasal hypothalamic lesions and have been reported to alter the subsequent feeding behavior and/or insulin levels of treated animals. In our previous studies bipiperidyl mustard alone had no effects on insulin levels or feeding, but in combination with glutamate produced hyperphagic obesity. Administration of exogenous cholecystokinin octapeptide also has been shown to affect feeding behavior and plasma insulin. In order to determine if endogenous cholecystokinin played a role in the effects of glutamate or bipiperidyl mustard, concentrations of cholecystokinin in the pituitary glands of lesioned rats were measured. Bipiperidyl mustard alone increased cholecystokinin content while combined lesioning with glutamate prevented the increase. The potential role of cholecystokinin-containing elements of the hypothalamus and pituitary in modulation of feeding is discussed.

Animals↗
PubMed1987

Effects of chronic delta-9-THC treatment on cardiac beta-adrenoceptors in rats.

This study was designed to determine if chronic treatment with delta-9-tetrahydrocannabinol (THC) alters cardiac beta-adrenoceptors in the rat. Following daily oral administration of 10 or 20 mg/kg THC or an equivalent volume of control solvent for 90 days, rats were sacrificed, and sarcolemmal membranes were prepared from ventricular myocardium. Beta-adrenoceptor density and binding affinity estimated with (-)[3H]dihydroalprenolol; a beta-adrenergic antagonist, were not significantly affected by treatment with THC when compared to vehicle controls. These results suggest that the tolerance to cardiovascular effects of THC which develops during chronic exposure in the rat is not associated with alterations in cardiac beta-adrenoceptors as monitored by radiolabeled antagonist binding.

Animals↗
PubMed1986

Components of hypothalamic obesity: bipiperidyl-mustard lesions add hyperphagia to monosodium glutamate-induced hyperinsulinemia.

Rats with bilateral electrolytic lesions in the general region of the ventromedial hypothalamic (VMH) nucleus develop hyperinsulinemia, excessive food intake and obesity. Monosodium glutamate (MSG) destroys neurons of the arcuate hypothalamic (AH) nucleus and produces hyperinsulinemic but hypophagic obesity. Bipiperidyl mustard (BPM) primarily destroys VMH neurons, but has produced only a slight obesity even when rats were maintained on high-fat diets. In the present study, rats treated with MSG (AH lesion) were hyperinsulinemic, moderately obese and hypophagic; BPM rats (primarily VMH lesion) were not different from controls when fed standard chow diets. However, MSG/BPM rats (AH + VMH lesion) were hyperinsulinemic, massively obese and hyperphagic. Thus, two components of the electrolytic lesion syndrome previously attributed to VMH damage (hyperinsulinemia and obesity) were reproduced simply by MSG treatment alone. The third component (hyperphagia) occurred only when both AH and VMH were lesioned, suggesting that neurons in both nuclei may perform a satiety function and may be able to substitute for one another in this respect. Since MSG treatment is required for all components of both obesity syndromes described here, this underscores the importance of MSG-sensitive neurons in mechanisms of obesity. The combined treatment approach also represents the first rat model of hyperinsulinemic, hyperphagic obesity that can be entirely produced by systemic administration of neurotoxins.

Animals↗
PubMed1986

Increase in hypothalamic cholecystokinin following acute and chronic morphine.

Recent evidence supports an antagonistic interaction between cholecystokinin (CCK) and opiate peptides. The present study determined the effects of various levels of morphine treatment on hypothalamic levels of CCK as determined by radioimmunoassay. Acute treatment with morphine sulfate (10 mg/kg) or implantation of one morphine pellet (75 mg free base) increased levels of CCK in whole hypothalamus. Increased exposure to morphine by either chronic injections or implantation of two pellets did not result in a further change in whole hypothalamic CCK levels. In samples dissected into hypothalamic subregions, the effect of morphine on CCK levels was localized to medial but not lateral or posterior regions. These experiments extend earlier in vitro findings and suggest that some of the physiological and behavioral effects of opiate peptides may result from modulation of endogenous CCK.

Animals↗
PubMed1986

Clonidine has a bidirectional effect on operant responding for food.

Clonidine, an alpha-noradrenergic agonist, has had inconsistent effects when administered peripherally in previous studies of feeding behavior. The present experiment was undertaken to evaluate clonidine using an operant feeding paradigm (continuous reinforcement schedule) to provide detailed data on the time course of its effects. Over an entire four-hour session, all doses of clonidine tested (25, 50, or 100 micrograms/kg) increased bar-pressing. The 50 micrograms/kg dose was most effective. An examination of the time course of responding revealed that the initial effect of clonidine was to decrease responses with the duration and magnitude of the decrease directly proportional to dose. However, clonidine also prolonged a phase of steady responding for food once the animals resumed bar-pressing, resulting in a net increase of food intake. Future investigations of clonidine should take into account the effects of increasing dose on delayed onset of feeding.

Animals↗
PubMed1974

Target structure and echo spectral discrimination by echolocating bats.

Echolocating bats can use sonar to discriminate among targets which reflect echoes differing in spectral distribution of energy but not in overall intensity. They can detect differences smaller than 1 millimeter in fine target structure. Bats may be capable of classifying targets from echo spectral signatures and might thus be able to distinguish among flying insect prey by sonar.

Animals↗
PubMedDate not supplied

Effects of conditioned fear and environmental novelty on plasma beta-endorphin in the rat.

The levels of rat plasma beta-endorphin-like immunoreactivity following a 30 min exposure to (1) an unfamiliar operant chamber, (2) an unfamiliar operant chamber providing a VI-5 second schedule of 3 mA, 1 sec footshocks, or (3) a familiar chamber providing no shocks, but previously paired with unavoidable shocks were compared to control values from animals left undisturbed in their familiar home cages. The shocked group showed ten-fold elevations of beta-endorphin-like immunoreactivity compared to the undisturbed control animals, while conditioned rats showed a smaller two-fold elevation when re-exposed to a chamber in which they had previously been shocked. Two of five rats exposed merely to an unfamiliar chamber showed elevations, but there was no statistically reliable group effect. Such procedures may be useful for controlled and parametric studies of the mobilization of pituitary or brain pools of beta-endorphin under conditions involving merely anticipation of pain rather than the actual activation of ascending nervous pain pathways.

Animals↗
PubMedDate not supplied

Shuttlebox avoidance in rhesus monkeys: effects on plasma cortisol and beta-endorphin.

Groups of monkeys either extensively pretrained to avoid shocks in a shuttlebox or with minimal prior experience were compared for plasma cortisol and beta-endorphin levels immediately following: (1) an exposure to the box with no shock, (2) the box providing repeated inescapable shocks or (3) a re-exposure to the box, again with no shock presentation. Mere exposure to the unfamiliar box elevated plasma cortisol just as much as exposure + shock did when inexperienced monkeys were tested. However, animals with a history of previously successful shock avoidance showed smaller elevations when exposed to the box alone, than they did when inescapable shock was received. Plasma beta-endorphin levels following shuttlebox exposure showed only a sporadic pattern of elevations in either inexperienced or pretrained monkeys. However, levels of beta-endorphin as determined under control conditions in the home cage were lower in pretrained animals, as were plasma levels of cortisol. The results indicate that behavioral factors may effect plasma cortisol and beta-endorphin following both acute and chronic shuttlebox experience.

Animals↗
PubMedDate not supplied

Satiety, hunger and regional brain content of cholecystokinin/gastrin and met-enkephalin immunoreactivity in sheep.

Cholecystokinin (CCK) and met-enkephalin (MEK) related peptides have been shown to alter feeding behavior subsequent to their injection into the peripheral circulation or directly into the brains of several species. To evaluate the potential role of endogenous brain pools of these peptides in feeding, groups of sheep were sacrificed either immediately following a meal (satiated) or after various intervals of food deprivation (hungry). Content of CCK-gastrin immunoreactivity in the anterior hypothalami of satiated sheep was elevated compared to 2, 4, or 24 hours of food deprivation. Content of MEK increased progressively with longer intervals of fasting (4 and 24 hours) in the amygdala and basomedial hypothalamus, whereas olfactory bulb content decreased with a similar time course. The results support a potential role for anterior hypothalamic CCK/gastrin in behaviors of satiety, whereas MEK neurons of limbic/rhinencephalic regions appear to form part of a separate circuit gradually activated by increasing hunger. Results are discussed in terms of potential target regions of the peptides, as well as the regional levels and feeding response of sheep as compared to available data from other species.

Amygdala↗
PubMedDate not supplied

Oral administration of 3,4-methylenedioxymethamphetamine (MDMA) produces selective serotonergic depletion in the nonhuman primate.

MDMA (3,4-methylenedioxymethamphetamine) has been reported to produce serotonergic depletion in nonhuman primates at doses as low as 2.5 mg/kg (1-2 times the typical human dose). The current study evaluated the dose-response relationships of MDMA (1.25-20.0 mg/kg) using regional concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and home cage behavior as endpoints. Adult female rhesus monkeys (n = 16) were treated orally with 0, 1.25, 2.5, or 20.0 mg/kg MDMA twice daily for 4 consecutive days. Eighteen behaviors were measured in the home cage prior to, during, and after MDMA treatment. One month after the last dose, the animals were sacrificed and brains dissected into several regions for neurochemical analyses. 5-HT and 5-HIAA were analyzed via HPLC/EC. The lower doses of MDMA (1.25 and 2.5 mg/kg) did not significantly alter 5-HT or 5-HIAA concentrations in any brain region except hippocampus in which 5-HT concentrations were decreased after 2.5 mg/kg. MDMA at 20.0 mg/kg significantly decreased 5-HT and 5-HIAA concentrations in several cortical and midbrain structures. However, 5-HT and 5-HIAA concentrations in brain stem and hypothalamus were not significantly altered after any dose of MDMA. Combined with previous data from this laboratory, these results indicate that the decreased concentrations of 5-HT and 5-HIAA in selected brain regions show a selective dose-response relationship for MDMA-induced neurotoxicity as measured by serotonergic depletion in the nonhuman primate.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Domoic acid: neurobehavioral and neurohistological effects of low-dose exposure in adult rats.

Adult rats treated IP with domoic acid at 0, 0.22, 0.65, or 1.32 mg/kg were tested for passive avoidance (PA), auditory startle (AS), or conditioned avoidance (CAR) behaviors. Clinical signs were observed only at the 1.32 mg/kg dose level. Within 24 h of dosing, rats surviving a dose of 1.32 mg/kg exhibited transient decreased body weight and exaggerated AS responding. Startle latency and habituation, PA, and CAR were not affected. Examination of brains from six rats per group revealed a subset (2/6) of animals receiving 1.32 mg/kg domoic acid with degenerating neurons in the hippocampal CA1/CA3 subregions and gliosis. The decreased body weight and increased startle suggest a hyperreactivity syndrome possibly related to neuronal degeneration in the hippocampus. In a separate experiment, domoic acid at an IP dose of 0.93 mg/kg was found to produce hypomotility in addition to a decrease in body weight. Both effects were reduced by pretreatment with scopolamine (2 mg/kg), but not with caffeine (30 mg/kg), indicating a possible cholinergic involvement in domoate's toxicity.

Acoustic Stimulation↗
PubMedDate not supplied

Gender-based differences in rats after chronic dietary exposure to genistein.

Gender-based differences can be observed from pharmacokinetic, behavioral, or anatomical assessments. No single assessment tool will provide a complete answer, but the use of a variety of indices, each with known gender-related outcome differences, can reveal agent-induced gender-based alterations. In a series of initial range-finding studies in rats conducted at the National Center for Toxicological Research (NCTR), the effects of dietary exposure to the weak estrogen, genistein, have been assessed using a number of techniques with validated gender-related outcome measures. The findings indicated that (1) the internal dose of genistein was higher in females than males after equivalent dietary exposure and this was consistent with the faster rate of genistein elimination in males; (2) in behavioral assessments, males and females in the high-dose dietary genistein group consumed more of a sodium-flavored solution; however, no genistein-related changes were observed in open field or running wheel activity, play behavior, or intake of a saccharin-flavored solution; and (3) dose-related alterations of the volume of the sexually dimorphic nucleus of the medial preoptic area were observed in genistein-exposed male rats but not females. These observations describe the utility of a variety of gender-based assessment tools and indicate that dose-related effects of developmental and chronic dietary exposure to genistein can be observed in the rodent. Additional studies, perhaps in nonhuman primates, are necessary to further predict the effect(s) of genistein on human gender-based development.

Administration, Oral↗