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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. This paper briefly reviews mechanisms by which such widely-used volatile anaesthetics as halothane and isoflurane suppress neural function in the brain. 2. In general, anaesthetics tend to depress neuronal firing and excitatory synaptic transmission, and potentiate synaptic inhibition. 3. According to recent evidence, a particular important action of anaesthetics is to inactivate a variety of both voltage-dependent and agonist-triggered Ca-currents. 4. Activation of K outward currents and Na inward currents probably occurs only with higher doses of anaesthetics. 5. How anaesthetics interfere with Ca-channels remains largely a matter of speculation--though some evidence favours a Ca-mediated action, following Ca2+ release from internal stores, that may account also for potentiation of IPSPs by prolonging the opening of GABA-activated Cl- channels. 6. Whatever its precise underlying mechanism, a suppression of Ca-influx into pre-synaptic terminals could well account for the depression of excitatory synaptic transmission.
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PMID:Cellular and synaptic actions of general anaesthetics. 148 32

3-alpha-Hydroxy-5-beta-pregnan-20-one [pregnanolone (PA)] and 3-beta-hydroxy-5-pregnen-20-one 3-sulfate [pregnenolone sulfate (PS)] are steroids that have been shown in biochemical studies to be active at the GABA-benzodiazepine-chloride receptor complex, Pa as a "barbiturate-like" agonist and PS as a "picrotoxin-like" antagonist. Since other compounds that are active at this site interact with the effects of pentobarbital and ethanol, the behavioral effects of these steroids alone and in combination with pentobarbital and ethanol were tested. Pa blocks the convulsions caused by pentylenetetrazole (PTZ) and increases motor activity when given alone in low doses. In combination with either pentobarbital or ethanol, it enhances the depression in motor activity, hypothermia, and hypnosis. In contrast, PS has no effect on PTZ convulsions and depresses motor activity by itself. With pentobarbital, PS enhances the depression in motor activity but has no effect on hypothermia or hypnosis. With ethanol, PS enhances the hypothermia but does not affect motor activity or hypnosis. Therefore, Pa and PS show different but not opposite effects in interacting with compounds active at the GABA-benzodiazepine-chloride receptor complex.
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PMID:Interaction of pregnanolone and pregnenolone sulfate with ethanol and pentobarbital. 151 42

In vivo voltammetry at electrochemically pretreated carbon fibre electrodes was used to investigate the effect of intracerebroventricular (i.c.v.) administration of N-methyl-D-aspartic acid (NMDA) on neuronal activity in rat nucleus accumbens. Infusion of a low dose of NMDA (1 nmol) was followed a few minutes later by rapid changes in both Peak 1 and Peak 2 heights indicating large but short-lived increases in the extracellular concentrations of ascorbate and catecholamines, respectively. These responses did not seem to be dependent on the dose infused since infusion of NMDA for a longer time period neither changed the amplitude nor the time-course of these effects. The increase in Peak 2 height was resistant to pargyline pretreatment indicating that this response mainly reflected the release of dopamine. The administration of NMDA was followed by behavioural activation in the animals but not convulsions. Co-administration of the competitive NMDA receptor antagonist, CPP (1 nmol), completely blocked these effects while the acetylcholine receptor antagonist, atropine (1.5 nmol), and the GABA receptor antagonist, picrotoxin (1 nmol), failed in this respect. The phenomenon spreading depression is discussed as a possible explanation of these results.
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PMID:Rapid changes in ascorbate and dopamine release in rat nucleus accumbens after intracerebroventricular administration of NMDA. 152 Nov 53

The purpose of this study was to determine which inhibitory pathway(s) mediate the alterations in the monosynaptic (MSR) and polysynaptic (PSR) reflexes after two different doses of physostigmine. It was found previously that 0.8 mg/kg physostigmine facilitated the MSR and 2.0 mg/kg initially depressed and then facilitated the MSR. Both doses facilitated the PSR. In this study, the animals were pretreated with either strychnine (0.1 mg/kg) or bicuculline (0.5 mg/kg), prior to the administration of either dose of physostigmine. It was found that both strychnine and bicuculline blocked the facilitation produced by the small dose of physostigmine, while bicuculline alone blocked the depression of the MSR produced by the large dose of physostigmine. Strychnine partially blocked the effects of both doses of physostigmine on the PSR, while bicuculline only partially blocked the effects of the small dose of physostigmine. These data suggest that the depression of the MSR was the result of a GABA-mediated pathway, while the facilitation of MSR involved both glycine and GABA.
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PMID:The role of GABA and glycine in the physostigmine-induced alterations of spinal cord reflexes. 154 1

We have evaluated the analgesic effect of continuous intrathecal administration of midazolam in 4 patients using a three-level score (no change, amelioration, and marked improvement). The secondary effects of this drug were also investigated (sedation, nausea, vomiting, respiratory depression, urinary retention, motor dysfunction). In one patient midazolam was the only drug administered, whereas in three patients this drug was associated with morphine. In one patient with a peripheral arteriopathy, midazolam at a dose of 12 mg/day was unable to equal the analgesic effect achieved with 0.4 mg of morphine. The remaining three patients had carcinoma and received a continuous intrathecal perfusion of morphine at increasing daily doses up to 12; 4,8; and 6 mg/day, respectively without pain relief. In these patients the association of midazolam at respective doses of 9; 4-8; and 6 mg/day induced amelioration in one patient and marked improvement in the two other patients. Midazolam did not change the heart rate, respiratory rate, arterial blood pressure, nor body temperature. We believe that the analgesic effect of intrathecal administration of midazolam is due to its coupling with the ionophore complex GABA-spinal benzodiazepine that in turn produces an increment of the GABA amino butyric acid at this level.
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PMID:[Intrathecal administration of morphine, midazolam, and their combination in 4 patients with chronic pain]. 159 51

Gamma-aminobutyric acid (GABA) levels in platelets were measured in 19 patients with migraine (7 males and 12 females, average age: 36.5 years) and 27 patients with chronic tension-type headache (TH; 9 males and 18 females, average age: 48.9 years). Twenty-one normal healthy volunteers composed the control group (11 males and 10 females, average age 34.9 years). The GABA levels in platelets were determined using high performance liquid chromatography with fluorescent detection (HPLC-FC). The GABA levels in platelets were 30.8 +/- 11.7 pmol/10(9) platelets (mean +/- S.D.) in the patients with migraine, 43.1 +/- 11.8 pmol/10(9) platelets in the patients with TH and 34.7 +/- 8.1 pmol/10(9) platelets in the healthy controls. The platelet GABA levels in the patients with TH were significantly higher than in the migraine patients and the healthy controls (p less than 0.05). The possible role of GABA in headache is discussed. We consider that TH may be a state of neuronal hyperexcitability similar to migraine and that GABA in the platelets of patients during TH attacks may be elevated to counterbalance it. Alternatively, we suggest that the rise of GABA levels in platelets is related to emotional factors, such as depression, in the TH patients. Further studies must be undertaken concerning the relationship between platelet GABA levels and headache.
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PMID:Platelet gamma-aminobutyric acid levels in migraine and tension-type headache. 162 59

The electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons were studied in slices from young (three to four months) and aged (25-32 months) Sprague-Dawley rats having previously performed two behavioral tasks. About 20% of the aged rats were impaired in either the spontaneous alternation task or the water maze task. Electrophysiological parameters were measured and compared in young and aged animals using intracellular recordings. No age-related differences were observed in membrane potential, input resistance, amplitude of action potentials or amplitude of calcium spikes. The amplitude and duration of individual afterhyperpolarizations following a single spike were unchanged. In contrast, the neuronal excitability was significantly decreased and the spike duration significantly enhanced in aged rats as compared to young rats. The comparison of afterhyperpolarizations (which follow a burst of spikes) between young and aged rats was more complex. An increase in the amplitude and duration of afterhyperpolarizations generally occurred in aged animals. However, this increase was not consistent among animals and was dependent on the holding potential of the neuron and on the number of action potentials used to trigger the afterhyperpolarization. The depolarizing effect of bath-applied carbachol, as well as the associated increase in membrane resistance were reduced in neurons from aged rats. In contrast, the effects of carbachol on the depression of synaptic events and the blockade of the afterhyperpolarizations were similar in young and aged animals. In addition, the amplitude of the slow cholinergic excitatory postsynaptic potential induced by stimulation of cholinergic afferents in the presence of physostigmine was also decreased in aged rats. Excitatory postsynaptic potentials and inhibitory postsynaptic potentials following electrical stimulation of stratum radiatum were compared. The amplitude and duration of excitatory postsynaptic potentials were increased in aged rats. The amplitude and duration of the fast inhibitory postsynaptic potential were not significantly affected in aged animals. In contrast, the duration of the slow inhibitory postsynaptic potential was decreased in aged rats. Since the mean baclofen-induced hyperpolarization was only slightly reduced in aged rats, the most likely explanation is a decrease in the release of GABA rather than an alteration in the postsynaptic response mediated by GABAB receptors. A statistically significant correlation was found between the degree of impairment in the spontaneous alternation task and the amplitude of the carbachol-induced depolarization.
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PMID:Alterations in the properties of hippocampal pyramidal neurons in the aged rat. 163 Jun 25

The mechanisms by which benzodiazepines produce muscle relaxation and respiratory depression are not known, but they may include actions on peripheral benzodiazepine receptors or central GABA receptors, or a direct action on airway smooth muscle may also be involved. We have compared, therefore, the effects of diazepam, flunitrazepam and midazolam on airway tone by measuring isometric tension of guineapig trachealis muscle. Cumulative concentrations of diazepam, flunitrazepam and midazolam caused concentration-dependent relaxation of resting tone in the tracheal smooth muscle with no significant differences in pD2 values (-log EC50--an index of potency) or intrinsic activities (% of maximum response) for relaxations for the three compounds. Pretreatment with propranolol 10(-6) mol litre-1, flumazenil 10(-7) and 10(-6) mol litre-1 or PK11195 10(-6) mol litre-1 had no effect on diazepam- or midazolam-induced relaxation. Diazepam 3 x 10(-6) mol litre-1 pretreatment shifted the concentration-response curves for acetylcholine, histamine and serotonin (5-HT) to the right by a factor of approximately 2. Flunitrazepam 3 x 10(-6) mol litre-1 pretreatment also shifted the curves for histamine and 5-HT similarly to the right, whereas midazolam pretreatment did not inhibit any agonist-induced contractions. These results suggest that benzodiazepines relax airway smooth muscle, not via neural pathways or central and peripheral benzodiazepine receptors, but by a direct action on airway smooth muscle.
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PMID:Comparison of the relaxant effects of diazepam, flunitrazepam and midazolam on airway smooth muscle. 163 6

Time- and dose-response studies were carried out on the effects of the monoamine oxidase-inhibiting antidepressant and antipanic drug phenelzine on GABA levels in rat whole brain. At a dose of 15 mg/kg i.p., phenelzine significantly elevated GABA levels at all time intervals studied (1, 2, 4, 8, 16, and 24 h). A further investigation indicated that this was a dose-dependent effect. The possible importance of GABA in the etiology and pharmacotherapy of depression and panic disorder is discussed.
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PMID:Effects of the antidepressant phenelzine on brain levels of gamma-aminobutyric acid (GABA). 164 82

The neurobehavioral responsivity to peripherally injected muscimol, a gamma-aminobutyric acid-A (GABA-A) agonist, was assessed in infant (14-day-old), weanling (20-day-old) and young adult (53-day-old) outbred male mice. In the first experiment, relatively high doses of muscimol (ranging from 0.05 to 0.40 mg/kg in developing and from 0.50 to 3 mg/kg in adult animals) were found to dose-dependently induced solid catalepsy and ataxia, evaluated 5 times at 20-min intervals. In the second experiment, the GABA agonist was injected in dose ranges which include relatively small concentrations in order to assess its excitatory properties, observable in adults, on rearing and locomotion in developing mice. It appeared that levels of rearing and especially locomotion were enhanced at the low doses (0.025 and 0.050 mg/kg in developing, and 1.3 and 1.9 mg/kg in adult mice) and inhibited at the higher ones (0.150 mg/kg in developing and 1.9 and 2.5 mg/kg in adult mice). This adult-like biphasic action of muscimol in developing mice--excitation at low and depression/sedation at high doses--strongly suggests a full maturation of the GABA-A-related behavioral functions at a period of ontogeny where adult-like locomotion emerges. Given that previous studies have shown that muscimol can biphasically affect behavioral activity in newborn murines as well, it is suggested that GABA-related behavioral functions mature near-monotonically during ontogeny, unlike those related to other major neurotransmitter systems.
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PMID:Adult-like biphasic neurobehavioral changes induced by a GABA-A agonist in infant and weanling mice. 166 Dec 11


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