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Biomedical subjects

A C Scallet

Publications and source records attributed to A C Scallet.

At least 55 records · Page 3Linked to original sources
PubMed1991

Detection of estrogen receptor (ER) in the rat brain using rat anti-ER monoclonal IgG with the unlabeled antibody method.

Application of Sternberger's unlabeled antibody enzyme method for detection of the estrogen receptor (ER) using a rat primary antibody with rat tissues has been discouraged, presumably because nonspecific staining of endogenous IgG was expected with the required anti-rat IgG bridging antibody. Because the blood-brain barrier greatly reduces immunoglobulin infiltration into the brain, we hypothesized that rat brain tissue could be specifically immunostained using rat IgG primary antibodies. A rat monoclonal anti-ER antibody (H222) specifically stained ERs in the brains of ovariectomized but not in ovariectomized estrogen-treated rats. In contrast, the uterus, a well-perfused target organ stained intensely in a nonspecific fashion. Dense populations of estrogen receptors were observed in the medial preoptic area, the bed nucleus of the stria terminalis, and the arcuate and ventromedial nuclei of the hypothalamus. A monoclonal rat IgG directed against alpha-tubulin labeled primarily cortical dendrites quite distinct from the neuronal nuclei that are the primary antigenic sites for the estrogen receptor antibody. These results confirm that the sensitive unlabeled antibody method can be applied to rat brain tissues, even when the primary antibody is rat IgG and that labeling of endogenous IgG may be used as a simple method to evaluate the integrity of the blood brain barrier.

Animals↗
PubMed1991

"Isolation stress" revisited: isolation-rearing effects depend on animal care methods.

Early reports of enhanced behavioral reactivity in isolation-reared rats attributed this syndrome to "isolation stress." In the studies reported here, this "isolation stress syndrome" was reliably obtained in adult rats reared from weaning in individual hanging metal cages. Such isolates showed behavioral and adrenocortical symptoms of profound fear during open-field testing, unlike group-housed controls or littermate isolates reared singly in plastic cages. Animals in hanging metal cages are never touched by human caretakers, whereas rats reared in plastic cages are picked up and put in clean cages twice weekly. Handling hanging-cage isolates twice weekly to model the handling associated with cage changes completely protected against this syndrome. Further, there was no hormonal, neurochemical or anatomical evidence of chronic stress even in hanging-cage isolates. Littermates housed in social groupings (three rats per plastic cage) also froze and defecated in the open field at rates comparable to hanging-cage isolates if they were the first animals to be tested from their social group cage. It is probable that odor cues from familiar cagemates in the open field protected socially reared animals tested subsequently from the same cage from this syndrome. It is concluded that isolates are not chronically stressed, and that rearing effects are the result of a complex interaction between prior handling, social experience and test conditions.

Animals↗
PubMed1991

Marijuana exposure and pulmonary alterations in primates.

As part of a large multidisciplinary study, we examined lungs from 24 periadolescent male rhesus monkeys that were sacrificed seven months after daily marijuana smoke inhalation of 12 months duration. Animals were divided into four exposure groups: A) high-dose (one marijuana cigarette 7 days/week), B) low-dose (one marijuana cigarette 2 days/week and sham smoke 5 days/week), C) placebo (one extracted marijuana cigarette 7 days/week), and D) sham (sham smoke 7 days/week). Lungs, removed intact, were formalin inflated, sectioned and examined. Several pathological alterations, including alveolitis, alveolar cell hyperplasia and granulomatous inflammation, were found with higher frequency in all cigarette-smoking groups. Other alterations, such as bronchiolitis, bronchiolar squamous metaplasia and interstitial fibrosis, were found most frequently in the marijuana-smoking groups. Alveolar cell hyperplasia with focal atypia was seen only in the marijuana-smoking animals. These changes represent mostly early alterations of small airways. Additional follow-up studies are needed to determine their long-term prognostic significance.

Animals↗
PubMed1991

Chronic marijuana smoke alters alveolar macrophage morphology and protein expression.

Male rhesus monkeys were subjected to chronic exposure to marijuana smoke. High dose animals (HI) were exposed 7 days/week to 1 MJ cigarette/day; low dose animals (LO) were exposed on 2 consecutive weekend days to 1 MJ cigarette/day; placebo animals (EM) were exposed to 1 ethanol-extracted MJ cigarette/day for 7 days/week; sham animals (SH) were exposed to sham smoking conditions 7 days/week. This regimen was maintained for 1 year and was followed by a 7 month rest period. Alveolar macrophages of animals exposed to the LO and HI dose smoking regimens exhibited irregular cell surface morphology, increased vacuolization, and a spherical conformation upon adherence to plastic. Gel protein profiles of purified macrophages from HI and LO animals showed marked differences in both constitutive and bacterial lipopolysaccharide-elicited protein expression when compared with those of macrophages from the EM or SH animals. These results indicate that chronic THC exposure alters macrophage morphology and protein expression to external stimuli even after a 7 month rest period.

Animals↗
PubMed1991

Neurotoxicology of cannabis and THC: a review of chronic exposure studies in animals.

Several laboratories have reported that chronic exposure to delta-9-tetrahydrocannabinol (THC) or marijuana extracts persistently altered the structure and function of the rat hippocampus, a paleocortical brain region involved with learning and memory processes in both rats and humans. Certain choices must be made in designing experiments to evaluate cannabis neurotoxicity, such as dose, route of administration, duration of exposure, age at onset of exposure, species of subjects, whether or how long to allow withdrawal, and which endpoints or biomarkers of neurotoxicity to measure. A review of the literature suggests that both age during exposure and duration of exposure may be critical determinants of neurotoxicity. Cannabinoid administration for at least three months (8-10% of a rat's lifespan) was required to produce neurotoxic effects in peripubertal rodents, which would be comparable to about three years exposure in rhesus monkeys and seven to ten years in humans. Studies of monkeys after up to 12 months of daily exposure have not consistently reported neurotoxicity, and the results of longer exposures have not yet been studied.

Animals↗
PubMed1991

Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.

THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Chronic marijuana smoke exposure in the rhesus monkey. I. Plasma cannabinoid and blood carboxyhemoglobin concentrations and clinical chemistry parameters.

This report is the first in a series about a large multidisciplinary study designed to determine whether chronic marijuana (MJ) smoke exposure results in residual behavioral and/or neuropathological alterations in the rhesus monkey. Prior to the initiation of a year of chronic MJ smoke exposure, 64 periadolescent male rhesus monkeys were trained for 1 year to perform five operant behavioral tasks and then divided, according to their performance in these tasks, into four exposure groups (n = 15-16/group): (1) a high dose (HI) group, exposed 7 days/week to the smoke of one standard MJ cigarette; (2) a low dose (LO) group, exposed on weekend days only to the smoke of a standard MJ cigarette; (3) an extracted MJ cigarette (EX) group, exposed 7 days/week to the smoke of one ethanol-extracted MJ cigarette; and (4) a sham group (SH), exposed 7 days/week to sham exposure conditions. Daily exposures for 1 year were accomplished using a mask that covered the subjects' nose and mouth. Average body weights (initially 3.7 +/- 0.5 kg, mean +/- SD) and rates of weight gain (approximately 0.1 kg/month) were the same for all groups throughout the entire experiment. During the first week of exposure, plasma concentrations of delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-THC in the HI group were 59 +/- 7 (mean +/- SE) and 5.5 +/- 1.5 ng/ml, respectively, 45 min after MJ smoke administration and did not change significantly at similar times after exposure throughout the remainder of the year. Whole blood carboxyhemoglobin levels increased to approximately 13% 1 min after exposure to smoke in either the MJ or the EX groups. Comparison of blood chemistry and hematology values before, during, and after exposure indicated no differences for most parameters. During exposure, lymphocytes, alkaline phosphatase and gamma-glutamyl transferase were depressed in the HI group compared to in the SH group. During exposure, aspartate aminotransferase was elevated for both the HI and EX groups, suggesting a general effect of smoke exposure. Because these effects were transient and remained within the range of reported normal values, these data indicate that long-term, experimental exposure to MJ smoke is feasible and does not compromise the general health of the rhesus monkey.

Alkaline Phosphatase↗
PubMed1991

Effect of trimethyltin on amino acid concentrations in different regions of the mouse brain.

Trimethyltin (TMT) is a neurotoxic compound known to cause marked alterations in brain chemistry. We have previously demonstrated that a single oral dose of TMT produced a dose-dependent decrease in muscarinic cholinergic receptors in mouse brain and significantly elevated glutamine in several regions of the rat brain. This study was designed to determine if TMT produced dose- and time-related alterations in amino acid concentrations in the adult male C57BL/6N mouse brain and in peripheral organs and plasma. In the dose-response study, TMT was administered orally as a single dose of 0, 0.5, 1.0, 3.0 or 5.0 mg/kg and animals were sacrificed 24 hr after treatment. In the time-course study, mice were dosed with TMT at 3.0 mg/kg and sacrificed 4, 12, 24, 48 or 96 hr after dosing. Amino acid concentrations were quantified by HPLC/EC following precolumn derivatization with o-phthalaldehyde-tert-butylthiol. TMT produced dose-dependent increases in aspartate, glutamine and glycine in the caudate nucleus (CN), frontal cortex (FC) and hippocampus (HIP) at 3.0 and 5.0 mg/kg. TMT at 3.0 mg/kg produced significant increases of aspartate in FC and HIP after 48 hr. Glutamine concentrations were significantly increased at 24 and 48 hr in HIP and at 48 hr in CN. Glycine and GABA concentrations were significantly increased at 48 and 96 hr respectively in the HIP. Glutamine was increased in plasma at 4 and 12 hr and in liver at 24 hr. Hyperammonemia occurred in plasma after 8 hr and continued through 24 hr and was accompanied by an increase in serum urea nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Interactions of MK-801 with glutamate-, glutamine- and methamphetamine-evoked release of [3H]dopamine from striatal slices.

The interactions of MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine], glutamate and glutamine with methamphetamine (METH)-evoked release of [3H]dopamine were assessed in vitro to determine whether MK-801 inhibition of METH neurotoxicity might be mediated presynaptically, and to evaluate the effects of glutamatergic stimulation on METH-evoked dopamine release. MK-801 inhibition of glutamate- or METH-evoked dopamine release might reduce synaptic dopamine levels during METH exposure and decrease the formation of 6-hydroxydopamine or other related neurotoxins. Without Mg++ present, 40 microM and 1 mM glutamate evoked a N-methyl-D-aspartate receptor-mediated [3H]dopamine and [3H]metabolite (tritium) release of 3 to 6 and 12 to 16% of total tritium stores, respectively, from striatal slices. With 1.50 mM Mg++ present, 10 mM glutamate alone or in combination with the dopamine uptake blocker nomifensine released only 2.1 or 4.2%, respectively, of total tritium stores, and release was only partially dependent on N-methyl-D-aspartate-type glutamate receptors. With or without 1.50 mM Mg++ present, 0.5 or 5 microM METH evoked a substantial release of tritium (5-8 or 12-21% of total stores, respectively). METH-evoked dopamine release was not affected by 5 microM MK-801 but METH-evoked release was additive with glutamate-evoked release. Without Mg++ present, 1 mM glutamine increased glutamate release and induced the release of [3H]dopamine and metabolites. Both 0.5 and 5 microM METH also increased tritium release with 1 mM glutamine present. When striatal slices were exposed to 5 microM METH this glutamine-evoked release of glutamate was increased more than 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Nutrition, neurotoxicants and age-related neurodegeneration.

The National Institute on Aging supports a program of investigation of "biomarkers" of aging (biological parameters that change in magnitude with age), some of which may be among the, as yet unknown, causes of Alzheimer's disease. Exposure to neurotoxicants can also produce symptoms similar to Alzheimer's disease and has been proposed as a causative factor. We have examined the role of dietary factors and age on Alzheimer's disease-like neurohistological and behavioral symptoms as well as on the neurochemical effects of treatment with a prototypical neurotoxicant, trimethyltin (TMT). We found that aging greatly increased the susceptibility of hippocampal neurons to TMT-induced neurodegeneration. Limiting the dietary intake of calories, which has been reported to slow the aging process, also reduced the neurotoxic effects of a given dose of TMT. Our current research focuses on the use of neurotoxins to model neurodegenerative conditions of aging in animals. We propose that by identifying an age-amplified biomarker or biomarkers somewhere along the chain from neurotoxic stimulus to neuronal necrosis we may also discover an up- or down-regulated gene, via it's gene product, that contributes to the etiology of human dementias. Our preliminary data suggest that up-regulated synthesis of post-synaptic glutamate receptors of the kainic acid-preferring subtype may be such a biomarker.

Aging↗
PubMed1989

Acute effects of marijuana smoke on complex operant behavior in rhesus monkeys.

The acute behavioral effects of marijuana smoke were assessed in rhesus monkeys using a battery of food-reinforced complex operant tasks that included incremental repeated acquisition (IRA, n = 9), conditioned position responding (CPR, n = 8), progressive ratio (PR, n = 8), delayed matching to sample (DMTS, n = 6), and temporal response differentiation responding (TRD, n = 3). Marijuana or placebo smoke was delivered by a specialized face mask 15-min before sessions at exposure levels of 1, 5, 10, and 15 puffs (35cc/puff) or one cigarette smoked to a butt length of approximately 10 mm (approximately 20 puffs). Marijuana smoke caused significant disruptions of performance in all tests except PR after exposure to 10 or more puffs. Generally, response rates decreased or latencies to respond increased. Performance in the PR test was not consistently affected by marijuana exposure. Accuracy of responding was not altered by marijuana smoke at doses lower than those that decreased response rates in the IRA or CPR tests. In the three animals performing under all five schedules, the relative sensitivities for detecting marijuana behavioral effects were DMTS = TRD greater than IRA = CPR greater than PR. These results suggest that performance under operant schedules that are thought to represent some aspect of time perception, short-term memory, learning, motivation, and position discrimination show differential sensitivity to disruption by marijuana smoke, a finding similar to that noted previously for iv THC administration.

Animals↗
PubMed1989

Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain.

THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects. Results from these experiments suggest that chronic exposure to THC does not produce significant alterations in catecholamine or indoleamine neurotransmitter systems or in opiate or GABA receptor systems in the rat brain.

Animals↗
PubMed1989

Behavioral and neurochemical effects of orally administered MDMA in the rodent and nonhuman primate.

MDMA (methylenedioxymethamphetamine) is a recreational drug of abuse known as "Ecstasy" which markedly decreases regional brain serotonin (5-HT) content and produces 5-HT nerve terminal degeneration in forebrain areas of the rat. In order to determine the acute and chronic behavioral effects of MDMA, adult rats were given MDMA at 0, 5 or 10 mg/kg, po for 4 consecutive days. Alternatively, parachloroamphetamine (PCA) at 5 mg/kg was administered under the same regimen. Within 30 min after the first dose, the MDMA-treated rats exhibited the serotonin motor syndrome consisting of straub tail and splayed hindlimbs comparable to that seen in the PCA-treated rats. This serotonin motor syndrome, with a duration of about 2 hr, was less pronounced after subsequent doses. At 2-4 wk after the last dose, no significant differences between control and treated rats were seen in emergence, hot plate response, auditory startle response or complex maze behavior even though a significant dose-related decrease (50%) in 5-HT concentration was observed in the frontal cortex and hippocampus of these rats 4 wks after the last dose. Adult female monkeys dosed po with 5 or 10 mg/kg of MDMA twice/day for 4 consecutive days demonstrated no spontaneous behavioral changes or weight loss compared to controls, but forebrain 5-HT concentration was reduced by 80% 1 mon after dosing. These data indicate that at doses only 2-3 times the human dose, MDMA produces significant forebrain 5-HT decreases but does not produce detectable residual behavioral alterations as assessed by these behavioral paradigms.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Benzodiazepine-like behavioral effects following withdrawal from chronic delta-9-tetrahydrocannabinol administration in rats.

Chronic exposure to cannabis extract or delta-9-tetrahydrocannabinol (THC) has been reported to produce hippocampal neuropathology in rats, as well as classical "hippocampal" behavioral deficits. In an attempt to replicate and extend these findings, male rats were exposed to THC for 13 consecutive weeks, beginning in early adolescence. Drugs were administered five consecutive days a week (Monday through Friday). There were five dose levels: vehicle control, 5, 10, or 20 mg/kg, p.o., and 20 mg/kg THC four days a week (Monday-Thursday), followed by 60 mg/kg on Friday. Following THC exposure, all animals were withdrawn from drugs for seven weeks prior to behavioral testing. Three behavioral tasks previously shown to be sensitive to hippocampal damage were assessed. These were habituation of open-field activity, 24-hr passive avoidance response retention, and complex maze performance. A fourth task, emergence latency, was also included because it has been determined to be sensitive to "anxiety" levels. To facilitate interpretation of the complex maze data, two additional experiments are also reported. One experiment tested rats exposed to trimethyltin (TMT, a potent hippocampal neurotoxicant) on the complex maze. The second assessed the affects of chronic/acute benzodiazepine (BZ) exposure upon maze performance. Test results did not suggest that chronic THC exposure produced behavioral deficits resembling those seen following hippocampal damage. Habituation rates in an activity monitor were identical for all exposure groups, and there was no passive avoidance retention deficit. Further, while TMT caused pronounced abnormalities in the complex maze, chronic THC exposure at the two highest dose levels significantly improved maze performance, similar to BZ effects on this task. Chronic THC also appeared to reduce freezing on the emergence task, another anxiolytic-like effect. These results support other reports of persistent long-term behavioral effects of chronic THC exposure. However, they suggest that some behavioral effects may more closely resemble the effects of minor tranquilizers rather than hippocampal damage.

Animals↗
PubMed1988

Determination of amino acids in different regions of the rat brain. Application to the acute effects of tetrahydrocannabinol (THC) and trimethyltin (TMT).

A modified HPLC method is described for the determination of amino acids [aspartic acid, glutamic acid, glutamine, glycine, taurine, and gamma-aminobutyric acid (GABA)] in brain tissue utilizing precolumn derivatization with o-phthalaldehyde (OPA)-tert-butyl-thiol and electrochemical detection. A simple extraction procedure was employed and DL-homoserine used as internal standard. A neurotoxin previously shown to affect brain amino acids (trimethyltin, TMT) and a psychoactive compound hypothesized to act on these neurochemicals (delta-9-tetrahydrocannabinol, THC) were administered to adult male rats and amino acids were measured. Results revealed a gradient of distribution of most amino acids, with lowest levels posteriorly in the brain stem and increasing to the highest values in anterior cortical regions. TMT increased glutamine significantly in all brain regions examined, but increased glycine and decreased taurine only in the frontal cortex and hippocampus. No significant changes in any amino acid were found in hippocampus after THC treatment. The results establish the validity and usefulness of this HPLC method for detecting neurotoxicity-related changes in brain amino acid metabolism.

Amino Acids↗
PubMed1988

Adrenocortical, beta-endorphin and behavioral responses to graded stressors in differentially reared rats.

Isolation rearing has long been suspected to alter hormonal and behavioral responses to stress. Two experiments were conducted to test the hypothesis that isolates are more timid or fearful than socially reared rats when exposed to novel test environments. In both, isolate response to 3 graded stressors was compared to that of socially-reared rats. In the first experiment, animals were handled, shocked or not treated prior to testing to produce three levels of conditioned fear. They were then tested on four paradigms previously shown sensitive to conditioned fear: open field activity, emergence latency, auditory startle, and latency to accept food from the experimenter. In the second experiment, rats were given a 0-, 5- or 20-min forced swim, then sacrificed for analysis of plasma corticosterone and pituitary and hypothalamic beta-endorphin. It was found that isolates showed little evidence of enhanced behavioral timidity, although rearing effects were seen on all 4 behavioral measures. Plasma corticosterone levels increased in a graded fashion over the course of the forced swim, but there was no effect of rearing conditions. While there were no effects of rearing or stress on hypothalamic beta-endorphin, pituitary beta-endorphin content was lower in females than in males, and isolate males had lower pituitary endorphin than social males. In summary, these experiments provide no evidence that isolation rearing produces a primary, global increase in fearfulness, but identify several behavioral and hormonal differences associated with differential housing in rats.

Animals↗
PubMed1988

Neurochemical and neurohistological alterations in the rat and monkey produced by orally administered methylenedioxymethamphetamine (MDMA).

MDMA is an amphetamine analog prescribed by some health professionals in the field of psychotherapy and used as a recreational drug by the general public. In recent reports, investigators have suggested that MDMA produces acute neurotoxicity when administered by subcutaneous injection. In order to determine if MDMA produces lasting neurochemical alterations after oral administration, groups of six rats (adult male Sprague-Dawley) were dosed by gavage with either 40 or 80 mg/kg of MDMA or saline vehicle once every 12 hr for 4 days. These rats were terminated 2 weeks after the first dose along with an additional group of rats (80 mg/kg) terminated 4 weeks after the first dose. Brain regions including the hippocampus (H), caudate nucleus (CN), hypothalamus (HY), frontal cortex (FC), and brain stem (BS) were analyzed by HPLC with electrochemical detection for concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine (NE). In the CN, 40 mg/kg MDMA produced no change in DA, DOPAC, or HVA, but a 50-60% decrease in 5-HT and 5-HIAA concentrations was observed at 2 weeks. Similar effects were observed at 80 mg/kg at both 2 weeks and 4 weeks. A temporary decrease was also seen in DA (21%) and in HVA (34%) 2 weeks but not 4 weeks after the 80 mg/kg dose regimen. In the H, MDMA (40 or 80 mg/kg) produced no change in NE, but a 50-60% decrease was seen in 5-HT and 5-HIAA concentrations at 2 weeks. Concentrations of 5-HT and 5-HIAA were significantly decreased in the HY and FC by all MDMA treatments, but DA and DOPAC concentrations were not altered as compared to vehicle controls. BS was least affected by treatment with no change in DA, DOPAC, or 5-HIAA concentrations and only a slight decrease in 5-HT (19-33%) concentrations at 2 weeks but not at 4 weeks. To determine the sensitivity of the nonhuman primate to MDMA, a total of nine rhesus monkeys were dosed with vehicle or 5 or 10 mg/kg MDMA (n = 3) by gastric intubation twice per day for 4 days. One month after MDMA dosing, a dose-related reduction from vehicle control values for 5-HT and 5-HIAA was observed. These results indicate that the monkey may be more sensitive than the rat to the persistent serotonergic neurotoxicity of MDMA.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Methylenedioxyamphetamine↗