Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied changes in plasma levels of neuroexcitatory amino acids during and between migraine attacks in 16 patients with migraine without aura, 11 with aura and 21 controls. Glutamic acid levels between attacks were 1.027 +/- 0.60 and 0.890 +/- 0.41 mg/dl in migraine patients without and with aura, respectively; during attacks the levels were 0.535 +/- 0.23 and 0.601 +/- 0.20 for the same patients. The concentration of glutamic acid in the control group was 0.980 +/- 0.64 mg/dl. Aspartic acid levels between attacks in patients without and with aura were 0.179 +/- 0.04 and 0.167 +/- 0.03 mg/dl. Concentrations during attacks were 0.129 +/- 0.02 and 0.119 +/- 0.02 mg/dl for the same patients. Plasma levels of aspartic acid for controls were 0.146 +/- 0.03 mg/dl. We found no significant variations in neuroexcitatory amino acids between migraine attacks in patients with an without aura; changes took place only during attacks, possibly related to the mechanisms of the spreading depression process.
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PMID:[Changes in neuroexcitatory amino acids during and between migraine attacks]. 820 47

Serotonin 5-hydroxytryptamine (5-HT)2 receptors are implicated in the etiology of mental disease and depression. Drugs that interact with the 5-HT2 receptor are used therapeutically to treat such illnesses, and their mechanisms of action are of great interest. In this study 5-HT2 receptor-ligand interactions were examined by site-directed mutagenesis in which three aspartic acid to asparagine mutants (Asn-120, Asn-155, and Asn-172) were created and expressed in NIH3T3 cells. The Asp-120 to asparagine mutant exhibited the same affinity for 125I-lysergic acid diethylamide (125I-LSD) as did the wild-type receptor and showed a decreased and GTP-insensitive binding affinity for the agonists 5-HT and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (approximately 10-fold) and the antagonists ketanserin and mianserin (approximately 10-fold) but not spiperone. The mutation also abolished agonist-stimulated formation of [3H]polyphosphoinositides (PI). The Asn-155 mutant showed reduced binding affinity for 125I-LSD (Kd, 2.8 nM versus 0.6 nM for the wild-type receptor) and had reduced affinity for agonists (approximately 30-fold) and for antagonists (14-75-fold). However, the Asn-155 receptor retained GTP sensitivity and the ability to stimulate PI formation. The Asn-172 mutant retained the wild-type Kd value for 125I-LSD, exhibited only approximately 5-fold reduced affinity for 5-HT and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane while retaining GTP-sensitive agonist binding showed no change in affinity for ketanserin, and had a small decrease in mianserin and spiperone binding (approximately 6-fold). The Asn-172 receptor also retained the ability to form PI. These results indicate that Asp-120 is necessary for allosteric activation of the guanine nucleotide-binding protein. Asp-155 is necessary for high affinity binding, probably by acting as a counterion for the amine group of the ligand. The different effects of the three mutations on ketanserin, mianserin, and spiperone binding affinity suggest that these antagonists may share overlapping but different binding domains. The information provided by this study may facilitate the design of therapeutic site-selective compound based on the structure of the 5-HT2 receptor.
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PMID:Site-directed mutagenesis of the serotonin 5-hydroxytrypamine2 receptor: identification of amino acids necessary for ligand binding and receptor activation. 831 24

Aspartic acid (580 mg/kg, SC) causes a long-lasting depression of ventilation in adult male, but not female rats. The purpose of these experiments was to determine if the aspartic acid-induced depression of ventilation in awake male Sprague-Dawley rats is a consequence of the release of endogenous opioids or somatostatin. These neuromodulators have been shown to cause depression of ventilation. Pretreatment of male rats with the opioid antagonist naloxone (5 mg/kg) 10 min prior to aspartic acid attenuated the drop of ventilation from -138.6 +/- 26.9 ml/min to -63.4 +/- 16.6 ml/min (p < 0.01) by affecting both tidal volume and frequency of breathing. Naloxone administered prior to saline had no effect on ventilation. In another experiment, cysteamine (100 mg/kg), a somatostatin depleter, injected SC 2 h before aspartic acid administration also attenuated depression of ventilation by affecting frequency of breathing. Cysteamine alone, compared to saline, had no effect on ventilation over 24 h. These results suggest that aspartic acid acts by releasing endogenous opioids and somatostatin.
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PMID:Cysteamine and naloxone attenuate aspartic acid-induced depression of ventilation. 877 56

Subcutaneous administration of aspartic acid results in a long-lasting but reversible depression of ventilation in male but not in female rats. Aspartic acid acts on N-methyl-D-aspartate receptors. The present study tested the hypothesis that a noncompetitive N-methyl-D-aspartate-receptor antagonist, dextromethorphan (Dex), would depress ventilation in female rats and stimulate it in male rats. Moreover, Dex administered prior to aspartic acid should prevent the aspartic acid-induced depression of ventilation in male rats. In female rats, Dex caused a 30% depression of ventilation relative to saline at 5 and 10 mg/kg (P < 0.01) but not at the highest dose (20 mg/kg). In male rats, Dex had no effect on ventilation. At a dose of 20 mg/kg, Dex depressed oxygen consumption to 50% of the saline value at all time points in female rats (P < 0.001) and in male rats 45 and 60 min after administration. The time points when Dex depressed ventilation and oxygen consumption were different in female rats, suggesting that the depression of ventilation was not the result of a depression in oxygen consumption. During a hypercapnic challenge (7% CO2), female rats treated with 5 and 10 mg/kg of Dex exhibited a smaller increase in ventilatory response relative to saline treatment. At a dose of 20 mg/kg, the hypercapnic responsiveness of male rats was markedly stimulated (85.8 +/- 8.95 ml/min) relative to saline (50.6 +/- 9.14 ml/min; P < 0.001). Finally, Dex administered before aspartic acid prevented the aspartic acid-induced depression of ventilation in male rats. Thus, in rats, Dex has gender-specific effects on ventilation and these effects are not associated with changes in oxygen consumption.
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PMID:Dextromethorphan affects ventilation differently in male and female rats. 894 9

Ventilation, oxygen consumption, the ventilatory equivalent for oxygen, and ventilatory responses to hypoxia and to hypercapnia were evaluated in conscious male rats who received each of four treatments: (1) microinjection of artificial cerebrospinal fluid (aCSF) into the arcuate nucleus and subcutaneously saline (CS); (2) aspartic acid into the arcuate nucleus and saline subcutaneously (AS); (3) aCSF into the arcuate nucleus and naloxone subcutaneously (CN); and (4) aspartic acid into the arcuate nucleus and naloxone subcutaneously (AN). Rats treated with CN exhibited a depression of ventilation, ventilatory equivalent, ventilatory response to hypercapnia, and tidal volume response to hypoxia and to hypercapnia. AS had no effect on any parameters. Administration of both aspartic acid and naloxone attenuated all the effects of CN except the depression of minute ventilation in response to hypercapnia. Therefore the naloxone (a mu opioid receptor antagonist) induced a depression of ventilation that was attenuated by aspartic acid acting on N-methyl-D-aspartic acid receptors in the arcuate nucleus.
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PMID:Aspartic acid in the arcuate nucleus attenuates the depressive effects of naloxone on ventilation. 986 84

Isolated porcine coronary arteries (PCA) contracted by depolarization with high K0 or by histamine (10 microM) were relaxed concentration-dependently by glutamic acid, aspartic acid, N-methyl-D-aspartate (NMDA) and, gamma-aminobutyric acid (GABA). In the PCA preparations contracted by high K0 or histamine the effects were monophasic, but the histamine-induced effects were more sustained and of larger amplitude. The ED50 values of cumulative concentration-response (CCR) curves obtained for the relaxation induced by L-glutamate in histamine-stimulated PCA preparations were shifted from 0.8 mM to 0.25 microM in presence of 1 mM glycine, a co-agonist required for the activation of NMDA receptors. The relaxations resulting from low-affinity binding of L-glutamic were dependent on Ca0 as evidenced by the shift of CCR curves to the right in the presence of 5-100 mM K0. In contrast, CCR curves obtained for contractions induced by NaF (1.5-12 mM), were significantly shifted to the left (from 6.3 to 3.1 mM). A depression of the maximum effect observed at higher F- concentrations was reversed by addition of 5 mM Mg0. Data show that glutamate induces a vasorelaxation that may be associated with symptoms seen in Chinese restaurant syndrome.
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PMID:Vasorelaxation induced by L-glutamate in porcine coronary arteries. 1133 34

Antidepressant activity of N-phenyl(benzyl)amino derivatives of aspartic acid was studied on various experimental models of depression. IEM-1770 (30 mg/kg) and IEM-1944 (20 mg/kg) exhibited antidepressant activity after single injection in the forced swimming and tail suspension tests. Antidepressant effect of 14-day administration of these compounds and reference drugs maprotiline (10 mg/kg) and citalopram (10 mg/kg) was confirmed on the model of learned helplessness.
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PMID:Antidepressant activity of aspartic acid derivatives. 1155 22

The striatum is a critical structure for the control of voluntary behaviour, and striatal synaptic plasticity has been implicated in instrumental learning. As ethanol consumption can cause impairments in cognition, learning, and action selection, it is important to understand the effects of this drug on striatal function. In this study we examined the effects of ethanol on long-term synaptic plasticity in the dorsomedial striatum (DMS), a striatal subregion that plays a central role in the acquisition and selection of goal-directed actions. Ethanol was found to impair N-methyl-d-aspartic acid receptor (NMDAR)-dependent long-term potentiation (LTP) dose-dependently in the DMS, and to promote long-term depression (LTD) at the highest concentration (50 mm) used. These results suggest that ethanol, at a concentration usually associated with mild intoxication, could significantly change experience-dependent modification of corticostriatal circuits underlying the learning of goal-directed instrumental actions.
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PMID:Ethanol reverses the direction of long-term synaptic plasticity in the dorsomedial striatum. 1755 91

Our previous study has reported that electroacupuncture (EA) at low frequency of 2 Hz had greater and more prolonged analgesic effects on mechanical allodynia and thermal hyperalgesia than that EA at high frequency of 100 Hz in rats with neuropathic pain. However, how EA at different frequencies produces distinct analgesic effects on neuropathic pain is unclear. Neuronal plastic changes in spinal cord might contribute to the development and maintenance of neuropathic pain. In the present study, we investigated changes of spinal synaptic plasticity in the development of neuropathic pain and its modulation by EA in rats with neuropathic pain. Field potentials of spinal dorsal horn neurons were recorded extracellularly in sham-operated rats and in rats with spinal nerve ligation (SNL). We found for the first time that the threshold for inducing long-term potentiation (LTP) of C-fiber-evoked potentials in dorsal horn was significantly lower in SNL rats than that in sham-operated rats. The threshold for evoking the C-fiber-evoked field potentials was also significantly lower, and the amplitude of the field potentials was higher in SNL rats as compared with those in the control rats. EA at low frequency of 2 Hz applied on acupoints ST 36 and SP 6, which was effective in treatment of neuropathic pain, induced long-term depression (LTD) of the C-fiber-evoked potentials in SNL rats. This effect could be blocked by N-methyl-d-aspartic acid (NMDA) receptor antagonist MK-801 and by opioid receptor antagonist naloxone. In contrast, EA at high frequency of 100 Hz, which was not effective in treatment of neuropathic pain, induced LTP in SNL rats but LTD in sham-operated rats. Unlike the 2 Hz EA-induced LTD in SNL rats, the 100 Hz EA-induced LTD in sham-operated rats was dependent on the endogenous GABAergic and serotonergic inhibitory system. Results from our present study suggest that (1) hyperexcitability in the spinal nociceptive synaptic transmission may occur after nerve injury, which may contribute to the development of neuropathic pain; (2) EA at low or high frequency has a different effect on modulating spinal synaptic plasticities in rats with neuropathic pain. The different modulation on spinal LTD or LTP by low- or high-frequency EA may be a potential mechanism of different analgesic effects of EA on neuropathic pain. LTD of synaptic strength in the spinal dorsal horn in SNL rats may contribute to the long-lasting analgesic effects of EA at 2 Hz.
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PMID:Long-term synaptic plasticity in the spinal dorsal horn and its modulation by electroacupuncture in rats with neuropathic pain. 1793 54

Opioids have been used for centuries to treat a variety of psychiatric conditions with much success. The so-called "opium cure" lost popularity in the early 1950s with the development of non-addictive tricyclic antidepressants and monoamine oxidase inhibitors. Nonetheless, recent literature supports the potent role of methadone, buprenorphine, tramadol, morphine, and other opioids as effective, durable, and rapid therapeutic agents for anxiety and depression. This article reviews the medical literature on the treatment of psychiatric disorders with opioids (notably, methadone and buprenorphine) in both the non-opioid-dependent population and in the opioid-dependent methadone maintenance population. The most recent neurotransmitter theories on the origin of depression and anxiety will be reviewed, including current information on the role of serotonin, N-Methyl d-Aspartate, glutamate, cortisol, catecholamine, and dopamine in psychiatric disorders. The observation that methadone maintenance patients with co-existing psychiatric morbidity (so called dual diagnosis patients) require substantially higher methadone dosages by between 20% and 50% will be explored and qualified. The role of methadone and other opioids as beneficial psychiatric medications that are independent of their drug abuse mitigating properties will be discussed. The mechanisms by which methadone and other opioids can favorably modulate the neurotransmitter systems controlling mood will also be discussed.
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PMID:Psychotherapeutic benefits of opioid agonist therapy. 1895 29


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