Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Oral administration of 3,4-methylenedioxymethamphetamine (MDMA) produces selective serotonergic depletion in the nonhuman primate. 768 72

The effects of the novel antidepressant tianeptine on behaviours induced by the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) and the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) were investigated. Tianeptine (10 mg/kg, i.p.) significantly attenuated wet dog shakes (WDS) induced by 5-HTP (75 mg/kg, i.p.; 30 min after carbidopa 25 mg/kg, i.p.). The effect was most marked when 5-HTP and tianeptine were given together. The main metabolite of tianeptine also attenuated WDS. Components of the 5-HT syndrome (i.e. reciprocal forepaw treading, hind limb abduction, flat body posture) induced by 8-OH-DPAT (0.5 mg/kg, s.c.) were unaffected by tianeptine and 5-HTP given both singly or together. However, tianeptine significantly reduced faecal pellet formation but not cage crossings resulting from 8-OH-DPAT administration. These cage crossings but not the associated faecal pellet formation were reduced by 5-HTP. This reduction was prevented by tianeptine. The increase of extracellular 5-HT in the frontal cortex following administration of 5-HTP was opposed and the concurrent increase of extracellular 5-hydroxyindoleacetic acid (5-HIAA) was enhanced by tianeptine. The above behavioural and neurochemical findings indicate that tianeptine opposes the increase of 5-HT at receptor sites due to 5-HTP administration.
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PMID:Behavioural and neurochemical evidence for the decrease of brain extracellular 5-HT by the antidepressant drug tianeptine. 769 70

This longitudinal study, extending over 12 months, assessed the behavioural and biochemical effects of hippocampal sympathetic ingrowth (HSI) into the partially denervated hippocampus. Male Long-Evans rats received fimbria-fornix lesions (FIFO) or sham operations at 90 days of age. At the same time half of the rats from each group sustained bilateral ablation of the superior cervical ganglia (SCGX). A battery of behavioural tests, measuring spontaneous alternation, activity in the open field and home cage, and radial-maze performance, were employed, starting after one very short (16 days) and one extended (216 days) post-operative delay. Neurochemical analyses measuring choline acetyltransferase (ChAT) activity, high-affinity choline (HACU) and noradrenaline uptake by hippocampal synaptosomes (HANU), hippocampal noradrenaline ([NA]), serotonin ([5-HT]) and 5-hydroxyindoleacetic acid ([5-HIAA]) concentrations were carried out in a dorsal, a "middle" and a ventral region of the hippocampus. Lesion of the FIFO induced a significant and enduring deficit in radial-maze performance, in addition to a persistent locomotor hyperactivity. ChAT and HACU were significantly depleted in all three regions of the hippocampus at 12 months, and these deficits were negatively correlated with maze performance. SCGX in the presence of the FIFO lesion significantly reduced [NA] in the middle region of the hippocampus, as compared to SCGX rats, and contributed to a restoration of lesion-induced depletions in [5-HT] and [5-HIAA] in the middle and ventral hippocampal regions, whilst failing to elicit any behavioural changes at either time point. It is concluded that if lesion-induced HSI indeed occurred, as is suggested by neurochemical evidence, it had no effect upon the observed behavioural deficits elicited by transection of the FIFO in the rat.
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PMID:Behavioural and neurochemical effects of superior cervical ganglionectomy in rats with septo-hippocampal lesions. 773 90

Previous experiments have shown that subjects which exhibit a high locomotor response to novelty (HR) also show a greater locomotor response to psychomotor stimulants than subjects which have a low locomotor response to a novel environment (LR). The current experiments were designed to examine in more detail the behavioral differences between HR and LR rats in non-drug paradigms. In the first experiment HR rats acquired schedule-induced polydipsia (SIP) more readily than LR rats. Panel pressing to gain access to the food pellets, however, was greater in LR rats compared to HR rats, especially after stable levels of SIP had been attained. In the second experiment one group of rats were fed daily after a 30-min period in photocell-cages (food conditioning; FC) while a control group was fed in the home-cage (non-conditioned; NC). FC subjects developed heightened locomotor activity in anticipation of feeding in the initial 30 min in the test-cage compared to NC rats. This anticipatory locomotor activity developed more rapidly and to a greater level in HR rats than in LR rats. The concentrations of dopamine, dihydroxyphenylacetic acid, homovanillic acid, serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were determined at the completion of behavioral testing in both the food conditioned and non-conditioned rats. The food conditioned experiment showed that variations in both the dopaminergic and serotoninergic systems may underlie individual differences in behavioral responsiveness. However, no clear pattern of neurochemical differences emerged. The current set of experiments have demonstrated differences between HR and LR rats in non-drug related paradigms and that HR rats appear to show a greater motivational excitement induced by periodic food delivery than LR rats.
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PMID:Individual differences in schedule-induced and conditioned behaviors. 791 72

(+/-)3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy"), an increasingly popular recreational drug, is known to damage brain serotonin (5-hydroxytryptamine [5-HT]) neurons, whilst also having a less pronounced effect on the dopaminergic system. Treatment with MDMA results in an increased locomotor activity, elevated basal serum corticosterone concentrations, decreased exploratory activity, and changes in body temperature. The aim of this study was to examine the dose related effects of subacute administration of MDMA (5, 10, and 20 mg/kg IP twice daily for 4 days) on home cage locomotor activity, "open field" and "step-down passive avoidance" behaviours, changes due to an 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) challenge, and on plasma corticosterone and brain neurotransmitter concentrations. Total locomotor activity counts were significantly increased by both 10 and 20 mg/kg MDMA for the 4 days of drug administration. There were no significant differences seen in the "open field" or "step down passive avoidance" behaviour, in the 8-OH-DPAT induced hypothermia, or in basal serum corticosterone concentrations. MDMA caused a significant depletion of both 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex and amygdala and a significant elevation of dopamine and noradrenaline in the hippocampus. Apart from the increase in locomotor activity following subacute administration, the observed behaviour of the MDMA treated rats would not appear to reflect the substantial changes in brain biogenic amine neurotransmitters.
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PMID:Some behavioural and neurochemical aspects of subacute (+/-)3,4-methylenedioxymethamphetamine administration in rats. 854 62

Rapid eye movement sleep deprivation (REMSD) is a potent stressor in rats. Behavioral abnormalities such as passive and active avoidance, locomotor activity, problem solving, sensory information processing, and the development of adaptive copping strategy in response to repeated stress are among the earliest obvious symptoms of REMSD, the mechanism for which remain largely unknown. The aim of this study was to determine whether 96 h of REMSD causes changes in monoamine neurotransmitters concentrations in rat forebrain regions (frontal cortex, FC; parietal cortex, PC, and striatum) that are involved in mediating higher brain functions such as attentional mechanisms, sensory information processing, and locomotor activity, which are severely affected in REMSD conditions. Rats were subjected to 96 h of REMSD using inverted flower pot water tank technique. To account for the stress associated with water tanks, a tank control group (TC) was included where the animals could reside comfortably on a large pedestal in the water tank. Regional brain concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenyacetic acid (DOPAC), L-3,4-dihydroxyphenylalanine (L-DOPA), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (HIAA) were determined by electrochemical detection using high-performance liquid chromatography. The concentrations of serotonin and its metabolite, HIAA, was reduced in the frontal and parietal cortexes of REMSD rats compared with TC or cage control (CC) group. NE, DA, DOPAC, and HVA concentrations in FC and PC of REMSD animals were remained unchanged compared with TC or CC rats. A significant increase in the concentrations of DA metabolites was observed in the striatum of REMSD rats when compared with CC and TC rats. There was a 29 and 31% increase in the concentration of striatal DA in REMSD group compared to the TC and CC groups, respectively; however, these percentages were not statistically different. Striatal NE, 5-HT, and HIAA concentrations were not significantly different among the three groups. These results suggest that 96 h of REMSD alters dopaminergic and serotonergic systems in different locations in rat brain. The effect of REMSD on the serotonergic systems are localized in the cerebral cortex, whereas dopaminergic metabolism is increased in the striatum.
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PMID:Changes in monoamines and their metabolite concentrations in REM sleep-deprived rat forebrain nuclei. 874 99

Developmental, biochemical, and behavioral concomitants of excessive alcohol consumption were investigated using a nonhuman primate model. The variables of interest were: (1) interindividual stability of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) from infancy to adulthood, (2) effect of parental deprivation early in life on adult CSF 5-HIAA concentrations; (3) correlations between CSF 5-HIAA and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations and alcohol consumption; and (4) correlation between the frequency of competent social behaviors and alcohol consumption. Twenty-nine rhesus macaques were reared for their first 6 months either with their mothers or without adults in peer-only conditions. At 6 and 50 months of age, each subject underwent a series of four, 4-day social separations. Cisternal CSF was sampled before and during the first and last separations; concomitantly, observational data were collected on social dominance behavior in the home-cage. When they reached 50 months of age, the monkeys were provided free access to a palatable alcohol solution daily for 1-hr periods before, during, and after the social separations. Before and after the 50-month separations, data were collected on all types of social behavior in the home-cage. Results showed that peer-reared subjects consumed more alcohol than mother-reared subjects during baseline conditions. Mother-reared subjects, however, increased their rates of consumption to equal peer-reared subjects' rates of consumption during the conditions of a social separation stressor. Peer-reared subjects also exhibited lower CSF 5-HIAA concentrations in infancy and adulthood than their mother-reared counterparts. With rearing condition held constant, interindividual differences in CSF 5-HIAA, MHPG, and homovanillic acid were stable from infancy to adulthood, and high rates of alcohol were consumed by the young adult monkeys with low CSF 5-HIAA and MHPG concentrations, particularly when the CSF was obtained during the social separations. High rates of alcohol consumption were also observed in subjects with infrequent social interactions and less competent social behaviors. In contrast to the human data, we found no gender differences in rates of alcohol consumption, nor in the correlations between alcohol consumption and the other variables. With some exceptions, findings from the study are generally consistent with predictions from Cloninger's type II model of excessive alcohol consumption in men with low CSF 5-HIAA, who also exhibit impaired impulse control and violent and antisocial behaviors.
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PMID:A nonhuman primate model of type II excessive alcohol consumption? Part 1. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and diminished social competence correlate with excessive alcohol consumption. 880 Mar 78

The purpose of this study was to develop an animal model for behavioral features of type II, early-onset alcohol abuse. To perform this research, cerebrospinal fluid (CSF) monoamine metabolite concentrations and home-cage social behaviors of 29 rhesus macaque subjects were examined in a 4-year longitudinal study. Half of the monkeys were reared for their first 6 months with their mothers, and the other half were reared without adults, instead with access only to monkeys of similar age. When the subjects were 6 months old, and again when they were 50 months old, they underwent a series of four, 4-day social separations. We obtained cisternal CSF before and during the first and last separation of each series to quantify 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylgycol (MHPG), and homovanillic acid concentrations. After the 6-month separations, subjects were placed into social groups, and social dominance rankings were assessed. Before and after the 50-month separations, social dominance rankings were evaluated again, and home-cage aggression and social behavior data were collected. Over the 3 1/2 years between CSF samplings, records were maintained of subjects' removal from their social groups for excessive aggression or treatment for wounding. Our results showed that among infants, reduced CSF 5-HIAA was correlated with low social dominance. As young adults, subjects from both rearing groups with low CSF 5-HIAA and MHPG concentrations exhibited reduced rates of social interaction and low social dominance rankings. In addition, peer-reared subjects with low CSF 5-HIAA concentrations exhibited inept social behaviors, and were frequently removed from their social groups for excessive aggression and deviant social behaviors. From these results, we conclude that the peer-rearing paradigm aggravates the untoward social consequences associated with low CSF 5-HIAA concentrations over and beyond reducing CSF 5-HIAA concentrations, suggesting that early experiences may contribute to CNS serotonin changes that increase the disposition to type II-related behaviors.
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PMID:A nonhuman primate model of type II alcoholism? Part 2. Diminished social competence and excessive aggression correlates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. 880 Mar 79

In the forebrain of the domestic chick (Gallus gallus domesticus), an area termed the mediorostral neostriatum/hyperstriatum ventrale is strongly involved in emotional learning paradigms such as acoustic filial imprinting. Furthermore, the involvement of the mediorostral neostriatum/hyperstriatum ventrale in stressful situations, such as social separation, has been demonstrated in 2-deoxyglucose studies. The aim of the present study was to examine whether quantitative changes of dopamine, serotonin and their metabolites occur during auditory filial imprinting and during social separation. Using in vivo microdialysis in tone-imprinted and in naive, control chicks, we compared the extracellular levels of homovanillic acid, a metabolite of dopamine, and 5-hydroxyindoleacetic acid, a metabolite of serotonin, during the presentation of the imprinting tone. A small, but statistically significant, decrease of extracellular homovanillic acid levels was found in the mediorostral neostriatum/hyperstriatum ventrale of imprinted chicks compared to control animals, whereas changes of 5-hydroxyindoleacetic acid were not detected. In a second experiment, we investigated the levels of homovanillic acid and 5-hydroxyindoleacetic acid in the mediorostral neostriatum/hyperstriatum ventrale of socially reared chicks during different stress situations, such as handling or separation from their cage mates. Handling induced a significant increase of homovanillic acid and 5-hydroxyindoleacetic acid, while social separation resulted in a significant increase of 5-hydroxyindoleacetic acid and only a slight increase of homovanillic acid. Despite considerable inter-individual variability, the increase of distress vocalizations (duration of distress calls) after social separation displayed a good correlation to the increased 5-hydroxyindoleacetic acid levels in all animals analysed. These results provide the first evidence that the physiological response of the mediorostral neostriatum/hyperstriatum ventrale related to different emotional conditions after acoustic imprinting and during stressful situations is, at least in part, mediated by dopaminergic and/or serotonergic pathways. Furthermore, the results from the present study indicate a distinct activation of dopaminergic and serotonergic pathways in relation to the behavioural situation and the associated changes of emotional status.
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PMID:Distinct activation of monoaminergic pathways in chick brain in relation to auditory imprinting and stressful situations: a microdialysis study. 913 59

The neurochemical consequences of aversive behavior based on novelty, rat social interaction, have been assessed in various rat brain regions utilizing high-performance liquid chromatography coupled with an electrochemical detector (HPLC-ECD) technique. The present studies indicated that compared to animals from the home cage, those exposed to the high-light aversive unfamiliar test condition, had significantly increased levels of 5-hydroxyindoleacetic acid (5-HIAA), the metabolite of 5-hydroxytryptamine (5-HT), in the tested brain regions including amygdala, entorhinal cortex, frontal cortex, temporal cortex, tuberculum olfactorium, hippocampus, nucleus accumbens, and striatum. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the metabolites of dopamine (DA), were increased in tuberculum olfactorium, nucleus accumbens, and striatum. When compared to the low-light familiar test condition (LF), the levels, following exposure to the highlight unfamiliar situation, of 5-HIAA were significantly increased in the amygdala, entorhinal cortex, tuberculum olfactorium, hippocampus, and nucleus accumbens, while the 5-HIAA levels remained unchanged in the frontal cortex, temporal cortex, and striatum. The DOPAC and HVA levels were also increased by the HU situation in the amygdala, tuberculum olfactorium, and nucleus accumbens. An increase was also found for the levels of DA in the amygdala. Such effects were prevented by diazepam or the 5-HT3 receptor antagonist ondansetron. It is concluded that the aversive test condition of the social interaction test (HU) increases 5-HT and DA turnover throughout the rat brain. Such effects might be related to the sensitivity to novel anxiolytic drug of the social interaction test.
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PMID:Effect of aversive stimulation on 5-hydroxytryptamine and dopamine metabolism in the rat brain. 932 72


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