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)

1. We examined the effects of gamma-aminobutyric acid (GABA) and baclofen on pre- and postsynaptic membrane conductances in dissociated rat hippocampal cells. Both GABA (5 microM with 10 microM-bicuculline) and baclofen (50 microM) caused small but significant increases in membrane conductance that were blocked by 2-hydroxysaclofen (100 microM), a GABAB receptor antagonist. This increase in membrane conductance seems to be mediated by GABAB receptors. 2. At a low concentration of GABA (1 microM) which has a very small direct postsynaptic effect on GABAA receptors, no postsynaptic GABAB effect was detected. However, at this concentration, GABA near maximally attenuated both excitatory and inhibitory synaptic currents. This GABA effect on transmitter release was significantly attenuated by 2-hydroxysaclofen. 3. Baclofen was also more potent in attenuating the inhibitory synaptic conductance than increasing postsynaptic conductance. Concentrations below 1 microM diminished synaptic currents by greater than 50%. At these low baclofen concentrations 2-hydroxysaclofen significantly attenuated baclofen's reduction of synaptic currents. 4. The effects of GABA and baclofen on synaptic conductances were blocked by pretreating the cultures with pertussis toxin, suggesting that a GTP-associated protein, Gi or Go is responsible for reducing transmitter release. 5. Despite the ability of GABA to diminish inhibitory synaptic currents through GABAB receptor activation, we observed no effect of 2-hydroxysaclofen on paired-pulse depression. Therefore, these presynaptic GABAB receptors may not be true 'autoreceptors'. 6. Our findings indicate that in culture, at least, the presynaptic GABAB effect responsible for synaptic modulation has a pharmacological profile similar to the postsynaptic GABAB effect. At present, it is unnecessary to postulate two different types of GABAB receptors.
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PMID:The modulation of rat hippocampal synaptic conductances by baclofen and gamma-aminobutyric acid. 166 62

1. The primary afferent neurons (dorsal cells) are of two types in lamprey, which are fast (touch) and slowly adapting (pressure), respectively. Intracellular stimulation of such sensory neurons evokes mono- and polysynaptic excitatory postsynaptic potentials (EPSPs) in spinobulbar neurons (giant interneurons) and in unidentified interneurons. Paired intracellular recordings between identified sensory cells and spinobulbar neurons made it possible to study the synaptic transmission in detail. It is shown that both touch and pressure primary afferents utilize excitatory amino acid (EAA) transmission and, furthermore, that these effects are subject to a presynaptic GABAB receptor modulation. 2. The monosynaptic mixed electrical and chemical EPSPs in giant interneurons had a mean peak amplitude of 3.2 +/- 1.3 (SD) mV, a time to peak of 4.7 +/- 1.2 ms, and a duration at one-half peak amplitude of 9.4 +/- 3.2 ms. Corresponding results were obtained with dorsal root or dorsal column stimulation. Seventy percent of the fast-adapting dorsal cells of the "touch" type evoked monosynaptic mixed EPSPs in giant interneurons, whereas only 3% of the slowly adapting "pressure" dorsal cells did. 3. The chemical part of the monosynaptic EPSPs evoked in giant interneurons was, in all cases tested, blocked by application of EAA antagonists, like the nonselective antagonist kynurenic acid (KYAC; 2 mM). The selective kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) had a similar effect, whereas the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphono-5-valeric acid (AP-5; 200-400 microM) did not change the EPSP, even in the absence of magnesium ions. 4. The monosynaptic excitatory synaptic transmission was modulated by application of the selective GABAB receptor agonist L-baclofen (5-10 mM local droplet application or 100-1,000 microM bath applied) or by gamma-aminobutyric acid (GABA; 100-1,000 microM), also when GABAA receptor-evoked effects were blocked by bicuculline (10 microM). L-baclofen or GABA in combination with bicuculline did not evoke any effects in the postsynaptic neuron on membrane potential, input resistance, or spike threshold. Therefore the effects of the GABAB receptor activation most likely occurs at the presynaptic afferent level. 5. In conclusion, the monosynaptic excitation from skin mechanoreceptors evoked in spinobulbar neurons is mediated by EAA receptors of the kainate/AMPA type. GABAB receptor activation causes a depression of this EPSP, most likely because of a presynaptic action. GABA interneurons are known to form close appositions on sensory axons in the lamprey.
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PMID:Primary afferents evoke excitatory amino acid receptor-mediated EPSPs that are modulated by presynaptic GABAB receptors in lamprey. 168 74

The chronic epileptic syndrome induced by injecting tetanus toxin into rat hippocampus causes functional changes that essentially are permanent, outlasting the period of active seizures by at least 1 year. These long-term changes have been characterized by an impaired performance on a range of behavioral tasks, which in turn have been associated with a physiologic depression of hippocampal evoked responses but not with any discernible histopathology. In the present study, we examined the hippocampi of rats in the postseizure phase of the tetanus toxin model and observed no significant changes in the concentration of neurochemical markers for six neurotransmitters. Therefore, the long-term reduction in hippocampal excitability cannot be attributed to any major loss of afferents or hippocampal neurons using aspartate, acetylcholine, gamma-aminobutyric acid (GABA), glutamate, norepinephrine (NE), or serotonin as their transmitters.
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PMID:Lack of change in neurochemical markers during the postepileptic phase of intrahippocampal tetanus toxin syndrome in rats. 170 Sep 50

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has been implicated in the pathophysiology of depression. Therefore, we examined cerebrospinal fluid (CSF) levels of GABA in depressed patients (N = 25) and normal controls (N = 20). There was no significant difference between the groups. However, among the depressed patients the subgroup of unipolar melancholic patients (N = 13) had significantly lower CSF levels of GABA than the rest of the depressed patients (N = 12). There was no significant difference for CSF levels of GABA between depressed patients who were (N = 14) or were not (N = 11) cortisol non-suppressors. It was of interest that among the controls there was a significant negative correlation between CSF levels of GABA and CSF levels of norepinephrine.
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PMID:CSF GABA in depressed patients and normal controls. 171 77

Diazepam binding inhibitor (DBI) is a neuromodulatory peptide for gamma-aminobutyric acid (GABA) neurotransmission. Levels of DBI in cerebrospinal fluid (CSF) were found to be elevated in depressed patients, when compared to age- and sex-matched normal controls. Levels of the peptide, corticotropin-releasing hormone (CRH), in CSF have been found to be elevated in depressed patients. Significant positive correlations between levels of DBI and CRH in the CSF of depressed patients and normal controls were found. These data suggest the possibility that DBI may have a role in coordinating responses to stress in humans, in addition to its possible role in the pathophysiology of depression.
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PMID:Cerebrospinal fluid diazepam binding inhibitor in depressed patients and normal controls. 178 40

Methohexital is an ultrashort-acting barbiturate widely used in dentistry because of its rapid onset, predictable effects, and short duration of action. Like other barbiturates, methohexital exerts its effects through the gamma-aminobutyric acid (GABA) receptor complex. By binding to its own receptor on the complex, methohexital augments the inhibitory effect of GABA on neurons and additionally can exert a similar effect independent of GABA. After intravenous injection, maximal brain concentrations are achieved within 30 sec and then quickly fall as the drug is redistributed to other tissues, yielding a duration of action after a single dose of 4 to 7 min. Hepatic metabolism accounts for elimination of the drug. Methohexital at conventional doses in healthy individuals is a mild respiratory depressant with modest cardiovascular effects. Adverse effects, however, can include apnea, cardiovascular depression, laryngospasm, hiccough, and allergic-like reactions. Although more recently introduced drugs, such as midazolam, etomidate, and propofol, have specific advantages, methohexital remains a drug of choice for dental outpatient anesthesia because of its low cost, rapid onset, short duration, lack of secretory or emetic properties, and proven history.
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PMID:Methohexital: a practical review for outpatient dental anesthesia. 184 56

Recent immunohistochemical studies have shown the distribution of histaminergic neurons in the mammalian brain, which are concentrated in the tuberomammillary nucleus of the posterior hypothalamus and project efferent fibers to almost all parts of the brain from the olfactory bulb to the spinal cord. Histaminergic neurons co-express other neuroactive substances, such as gamma-aminobutyric acid, adenosine, substance P, galanin and Met-enkephalin-Arg-Phe. In addition, pharmacological studies have demonstrated the presence of presynaptic histamine H3-receptors (autoreceptor) in addition to H1- and H2-receptors. The specific agonist (alpha-methylhistamine) and antagonist (thioperamide) of H3-receptors were developed. Results from a number of studies indicate a variety of physiological roles of neuronal histamine such as thermoregulation, feeding behavior, sexual activity, sleep-wakefulness cycle, hormonal regulation and so on. Moreover, histaminergic drugs affect not only the emotional behavior, but also are effective to treat some patients of depression, Parkinson's disease, akathisia, motion sickness and so on. The central histaminergic neuron system is also affected by mental disorders and neuropsychopharmacological drugs. This review especially focused on these points and suggests that the central histaminergic neuron system may play an important role in the regulation of mental functions.
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PMID:[Recent advances in neuropsychopharmacology of the central histaminergic neuron system]. 192 57

Selective antagonism of serotonin (5-hydroxytryptamine, 5HT) and noradrenaline transport by antidepressants is a key element in the 'amine' hypothesis of affective disorders. Uptake and/or transport sites of 5HT have been reported to be reduced in platelets of patients suffering from depression and in post-mortem brain samples of depressed patients and suicide victims. To date there has been little molecular information available on the structure and regulation of 5HT transporters. Using the polymerase chain reaction with degenerate oligonucleotides derived from two highly conserved regions of the transporters for noradrenaline and gamma-aminobutyric acid (GABA), we have identified a large family of related gene products expressed in rodent brain. One of these products hybridizes to a single 3.7-kilobase RNA restricted to rat midbrain and brainstem, where it is highly enriched within the serotonergic raphe complex. Transfection with a single 2.3-kilobase brainstem complementary DNA clone is sufficient to confer expression of a Na(+)-dependent 5HT transporter upon nonneural cells, with transport selectively and potently antagonized by 5HT uptake-specific antidepressants, including paroxetine, citalopram and fluoxetine.
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PMID:Cloning and expression of a functional serotonin transporter from rat brain. 194 72

The effect of somatostatin-14 (SS-14) on gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission in the dorsolateral septal nucleus (DLSN) was investigated using a submerged slice preparation and intracellular recording techniques. Somatostatin-14 applied by superfusion or by pressure ejection from micropipettes predominantly inhibited the intracellularly recorded fast inhibitory postsynaptic potential (fIPSP) and late hyperpolarizing potential (LHP) elicited by focal electrical stimulation of the DLSN. The decreases in LHP and fIPSP amplitude occurred at low concentrations of peptide, in the absence of appreciable changes in the passive-membrane properties of postsynaptic neurons, and outlasted the membrane hyperpolarizing effect produced by SS-14 at higher concentrations. The ability of SS-14 to modulate postsynaptic GABA receptor responses underlying the fIPSP and LHP were investigated by applying baclofen, a selective GABAB receptor agonist, and isoguvacine, a selective GABAA receptor agonist, by pressure ejection. Hyperpolarizing responses to GABAA and GABAB receptor stimulation were significantly decreased during superfusion of SS-14. Tetrodotoxin applied by superfusion blocked electrically evoked synaptic potentials but not the depressant effect of SS-14 on baclofen- or isoguvacine-induced hyperpolarization. Facilitation of the fIPSP or LHP by SS-14 also occurred but less frequently and consistently than the depressant action. Excitatory postsynaptic potentials and membrane response to NMDA or quisqualate appeared unaltered by bath-applied SS-14. These findings suggest a novel postsynaptic action of SS-14 leading to depression of synaptic responses mediated by GABAA and GABAB receptors. Synaptically released SS-14 in the DLSN may participate in modulation of feedforward and/or feedback inhibitory mechanisms coordinating DLSN function in the septo-hippocampal system.
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PMID:Somatostatin depresses GABA receptor-mediated inhibition in the rat dorsolateral septal nucleus. 197 66

1. The effects of general anaesthetics were investigated on neuronal sensitivities to transmitter substances, which were determined by iontophoretic applications of acetylcholine, glutamate, N-methyl-D-aspartate (NMDA) and gamma-aminobutyrate (GABA) during intracellular recording in in vitro slice preparations of neocortex (guinea-pig). 2. In most of the 65 neurones studied, perfusion of isoflurane (0.5-2.5 minimum alveolar concentration (MAC)) or Althesin (25-200 microM) and, in some cases, halothane (0.5-2 MAC), markedly reduced the depolarizing responses and associated membrane conductance changes evoked by dendritic applications of acetylcholine, glutamate, NMDA and GABA. 3. The order of depression was acetylcholine greater than glutamate or NMDA much greater than GABA. This selectivity could also be assessed from the EC50 for the isoflurane-induced depression of the just-maximal responses to acetylcholine, which was 0.9 MAC compared with an EC50 = 1.9 MAC for the suppression of glutamate responses. The selectivity was less pronounced in the case of the actions of Althesin, where the EC50s were 75 microM for the depression of acetylcholine responses and 90 microM for the depression of glutamate responses. 4. The hyperpolarizing responses observed when GABA was applied near the perikaryon in 7 neurones, were slightly reduced (approximately 15%) in 4, and unchanged in 3 neurones during anaesthetic application. 5. The pronounced depression of the responsiveness to the putative arousal transmitters and an observed blockade of acetylcholine-induced potentiation of glutamate actions suggest that anaesthetics produce unconsciousness, at least in part, by interfering with subsynaptic mechanisms of neocortical activation.
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PMID:Anaesthetic suppression of transmitter actions in neocortex. 198 Aug 37


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