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)

The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists dizocilpine and phenycyclidine, the competitive NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the antagonist at the glycine modulatory site of the NMDA receptor, 3-amino-1-hydroxy-2-pyrrolidone (HA-966) on the long lasting attenuation of some post-synaptic 5-HT1A receptor-mediated responses in rats (increased corticosterone secretion and inhibition of the cage leaving response) produced by a single injection of the 5-hydroxytryptamine1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was studied. It was found that these antagonists counteracted the attenuation of these responses at dose levels known to block the NMDA receptor-ion channel complex in vivo. It is concluded that the long lasting attenuation of postsynaptic responses after a 5-HT1A receptor agonist is initiated through stimulation of glutamate NMDA receptors indicating a functional interaction between the 5-HT and glutamate systems in at least two different models.
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PMID:N-methyl-D-aspartate receptor antagonists counteract the long lasting 5-HT1A receptor-induced attenuation of postsynaptic responses in the rat in vivo. 128 Mar 36

Male rats, aged 17 weeks at the end of experiments, were divided into four groups. Two groups lived in normal cage conditions with or without extra load (20% of the body weight) and two groups were trained by running with or without extra load for 8 weeks. Oxidation rates of succinate, glutamate + malate, palmitoylcarnitine, and pyruvate, and the activities of lactate dehydrogenase, citrate synthase, isocitrate dehydrogenase and cytochrome oxidase were measured in homogenates of the right ventricle and in those of the subendocardial and subepicardial layers of the left ventricle. Oxidation rates of succinate and palmitoylcarnitine tended to be higher in the subendocardium than in the subepicardium of sedentary control animals (p less than 0.1 and p less than 0.05, respectively). Transmural differences of succinate and palmitoylcarnitine oxidation rates were even more clear after running training (p less than 0.01 and p less than 0.05, respectively), after carrying extra load (p less than 0.001 and p less than 0.001, respectively) and after training carrying extra load (p less than 0.001 and p less than 0.05, respectively). Training also enhanced pyruvate oxidation rate in the subendocardium. Oxidation rates of all substrates were lower in the right ventricle than in the left ventricle. In control animals there were no regional differences in the myocardial enzyme activities and the training- or extra-load-induced changes were modest compared with the changes in the oxidation rates. The most significant change was the training-induced enhancement in the lactate dehydrogenase activity of the subendocardium (p less than 0.001 vs subepicardium). These results show greater subendocardial than subepicardial oxidation rates of certain substrates in the normal heart. These results also suggest that the myocardium adapts to increased work by increasing the subendocardial oxidation rate of some but not all substrates, indicating further that there may be qualitative mitochondrial differences in the different regions of the heart.
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PMID:Regional differences of substrate oxidation capacity in rat hearts: effects of extra load and endurance training. 207 98

In unanesthetized and unrestrained rats, microinjection of L-glutamate into the posterior hypothalamus produced hypertension and tachycardia. These cardiovascular responses were mostly accompanied with behavioral excitation such as searching the cage, rearing and sniffing. The cardiovascular responses elicited by L-glutamate were attenuated by prior injection with propranolol and hexamethonium but not with glutamate diethylester, phentolamine and atropine. The behavioral responses to L-glutamate were suppressed by propranolol, hexamethonium and phentolamine. These results suggest that catecholaminergic and/or cholinergic systems in the posterior hypothalamus may be involved in the mediation of the cardiovascular and behavioral responses induced by L-glutamate.
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PMID:Effect of L-glutamate, injected into the posterior hypothalamus, on blood pressure and heart rate in unanesthetized and unrestrained rats. 286 99

Neurotoxic doses of monosodium glutamate were administered to neonatal male and female Sprague-Dawley rats for five days postpartum. The rats were tested at 6 months for alterations in two forms of activity--initial activity in an open field and overnight activity in a familiar cage. In comparison with age-, sex- and handling-matched littermate controls, experimental subjects exhibited increased open field behaviors and reduced overnight activity. Subsequent histology indicated marked reductions in arcuate and periarcuate cells which included but probably were not limited to beta-endorphin containing neurons. These findings indicate that neonatal MSG has long-term behavioral and neurological consequences, that some changes occur within behaviorally discrete systems, and that they may be associated with functional alterations within endogenous opioid systems, inter alia.
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PMID:Neonatal monosodium glutamate differentially alters two models of behavioral activity in conjunction with reduced hypothalamic endorphins. 631 4

Effect alterations of methamphetamine by pretreatment of amino acids or their salts on ambulatory activity in mice were investigated to confirm a fact that certain amino acids, particularly monosodium L-glutamate, are added to methamphetamine by the street users, and that the amino acids augment the effect of methamphetamine. The ambulatory activity of mouse was measured by a tilting-type round activity cage of 25 cm in diameter. The amino acids or their salts tested were monosodium L-glutamate, monosodium L-aspartate, gamma-amino-butyric acid, L-alanine, L-lysine hydrochloride and L-arginine hydrochloride. A single administration of each chemical at doses of 1 and 2 g/kg i.p. did not induce a marked change in the ambulatory activity in mice. Methamphetamine 2 mg/kg s.c. induced an increase in the ambulatory activity with a peak at 40 min after the administration, and the increased ambulatory activity persisted for 3 hr. The ambulation-increasing effect of methamphetamine was augmented by the pretreatment of monosodium L-glutamate and monosodium L-aspartate at 30 min before the methamphetamine administration, while attenuated by the pretreatment of L-lysine hydrochloride and L-arginine hydrochloride in a dose-dependent manner. Gamma-aminobutyric acid and L-alanine did not affect the effect of methamphetamine. Similar augmentation and attenuation in the ambulation-increasing effect of methamphetamine were induced by the pretreatment of sodium bicarbonate 0.9 g/kg i.p. (urinary alkalizer) and ammonium chloride 0.07 g/kg i.p. (urinary acidifier), respectively. The urinary pH level was elevated by the administration of monosodium L-glutamate, monosodium L-aspartate and sodium bicarbonate, and decreased by L-lysine hydrochloride, L-arginine hydrochloride and ammonium chloride. Gamma-aminobutyric acid and L-alanine did not elicit a marked change in the urinary pH level. The present experiment confirms the fact in human that monosodium L-glutamate augments the effect of methamphetamine. Moreover, the present results suggest that monosodium salts of acidic amino acids augment, and conversely monohydrochloric salts of basic amino acids attenuate the effect of methamphetamine. The alterations of the ambulation-increasing effect of methamphetamine may be due to the urinary excretion rates of the drug through changes in the urinary pH level after the administration of amino acids or their salts.
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PMID:Effect alteration of methamphetamine by amino acids or their salts on ambulatory activity in mice. 687 1

The present experiments examined the role of excitatory amino acid receptors in the orofacial stereotypy induced by direct amphetamine microinjection into the ventrolateral striatum. In these experiments, the influence of prior intra-ventrolateral striatum treatment with various excitatory amino acid antagonists on the expression of amphetamine-stimulated oral stereotypy was observed. In all experiments, behavioral observations were conducted in the home cage using a time-sampling procedure. In the first experiment, different groups of rats received bilateral microinfusions of either kynurenic acid, 2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline or dizocilpine maleate. The excitatory amino acid antagonists were administered immediately prior to bilateral microinfusions of d-amphetamine. Both N-methyl-D-aspartate and non-N-methyl-D-aspartate antagonists dose-dependently attenuated or blocked the expression of dopamine-mediated stereotypy. 2-Amino-5-phosphonopentanoic acid was the most potent of these compounds, totally suppressing stereotypy at a dose of 0.3 micrograms (equivalent to 1.5 nmol). In the second experiment, the same compounds were tested for their ability to suppress physostigmine-induced mouth movements. Cholinergic stimulation of the ventrolateral striatum has previously been shown to elicit non-directed mouth movements, quite distinguishable from stimulus-directed, amphetamine-induced biting. Excitatory amino acid antagonists were administered in the same doses prior to bilateral infusion of physostigmine (2.5 micrograms/0.5 microliters). The expression of physostigmine-induced mouth movements was for the most part not affected by excitatory amino acid antagonists, although dizocilpine maleate slightly reduced this oral behavior. In a third experiment, behavior was observed following infusion of the antagonists alone, using the same doses as in the previous experiments. No behavioral alterations were observed with the exception of a small increase in nonspecific mouth movements induced by kynurenic acid and 2-amino-5-phosphonopentanoic acid. These findings indicate that the expression of dopamine-mediated oral stereotypy, induced by amphetamine stimulation of the ventrolateral striatal region, is highly dependent on activation of striatal excitatory amino acid receptors. In contrast, oral behavior induced by cholinergic stimulation of the ventrolateral region is not mediated by glutamate input. These results are discussed in relation to the synaptic organization of neuronal elements within the striatum. Moreover, the relevance to further understanding of orofacial dyskinesias is noted.
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PMID:Excitatory amino acid receptors mediate the orofacial stereotypy elicited by dopaminergic stimulation of the ventrolateral striatum. 791 60

In vivo microdialysis combined with HPLC-EC analysis was used to monitor extracellular glutamate and GABA in the medial nucleus accumbens of Lister hooded rats during acquisition and expression of a conditioned emotional response. Footshock paired with tone (acquisition of conditioned emotional response) causes a significant decrease in extracellular glutamate during the period of footshock followed by a marked, but short lasting increase when the rats return to their home cage. Expression of the conditioned emotional response on exposure to the contextual cue produces no change in glutamate during exposure to the contextual cue, but a short lasting increase after. Thus, both the conditioned emotional response and footshock are associated with marked, but short lasting, increases in extracellular glutamate in the nucleus accumbens which, in both cases, occurred after the aversive stimuli, i.e., when the rats are returned to their home cage. In contrast, when control rats are exposed to the testing box without giving footshock there is an increase in extracellular glutamate during the exposure period and this is accompanied by exploratory behaviour. The conditioned emotional response (contextual cue), footshock and exposure of the control rats to the test box all resulted in increased extracellular GABA during exposure to the test situation. These results suggest that increases in extracellular glutamate in the medial nucleus accumbens caused by the conditioned emotional response or footshock are probably associated with relief from, rather than response to danger.
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PMID:Extracellular glutamate in the nucleus accumbens during a conditioned emotional response in the rat. 858 69

Neural connections from the hippocampus and nucleus accumbens to the subpallidal area have been implicated by behavioral observation. The locomotor activity recorded in an automated activity cage increased substantially after the bilateral injection of carbachol, a cholinergic agonist, into the dentate gyrus of the hippocampus, and this increase of activity was reduced significantly after the injection of glutamate antagonist into the nucleus accumbens. On the other hand, this hyperactivity elicited by the injection of carbachol was also reduced by the injection of GABA into the subpallidal area. In another observation, increased locomotor activity was recorded following the injection of dopamine into the nucleus accumbens. However, the increase of locomotor activity induced by dopamine was attenuated by the injection of GABA into the subpallidal area. These observations suggest that neural connections from hippocampus and nucleus accumbens to the subpallidal region may contribute to locomotor activity.
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PMID:Neural connection from hippocampus to nucleus accumbens and the subpallidal area and their contribution to locomotor activity. 869 95

Two behavioral experiments were conducted in rats to evaluate the context-specificity of changes in nucleus accumbens glutamate transmission induced by systemic cocaine administration. At 2 weeks of withdrawal from daily cocaine injections (15 mg/kg, IP, daily x 7 days), subjects who had received cocaine in the test environment displayed a significantly greater motor response to intra-accumbens infusion of the glutamate receptor subtype-specific agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) than subjects who had received daily saline injections. Subjects who previously received cocaine in the home cage displayed no greater AMPA-induced motor activity within the test environment than saline-treated controls. In contrast, behavioral sensitization to an intra-accumbens challenge with the NMDA receptor-specific agonist, 1-aminocyclobutane-cis-1,3-dicarboxylic acid (cis-ACDA), was seen in both cocaine-treated subject groups. These results suggest that behavioral sensitization to psychostimulants may be mediated, in part, by a context-conditioned behavioral sensitization to glutamate transmission in the nucleus accumbens through AMPA/kainate receptors.
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PMID:Context-specific cross-sensitization between systemic cocaine and intra-accumbens AMPA infusion in the rat. 892 75

Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.
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PMID:Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains. 898 96


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