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. The effects of hypomagnesia on the neuronal responses induced by iontophorectically applied acetylcholine, glutamate, N-methylaspartate (NMDA) and gamma-aminobutyric acid (GABA) were investigated using intracellular recording techniques in in vitro slices of sensorimotor cortex (guinea-pigs). 2. Perfusion with Mg-free media, with or without tetrodotoxin (TTX), induced a small hyperpolarization (approximately 4 mV) and a small decrease (approximately 10%) in the input resistance of neurones. During TTX-blockade of Na-spike genesis, spontaneous depolarizing waves of low frequencies were observed in neurones of slices under Mg-free conditions. 3. The effects of acetylcholine and to a lesser extent, GABA actions, were depressed in a dose-dependent, reversible manner by decreases in the [Mg2+] of the perfusing media. In neurones of slices that had been incubated in Mg-free artificial cerebrospinal fluid to ensure a maximal depletion, the responses to these transmitters were potentiated by each sequentially administered increase in extracellular [Mg2+]. The actions of NMDA were potentiated during perfusion of Mg-free media. However, the responses to glutamate, which may activate receptors for NMDA, were either depressed or unchanged under these conditions. 4. A regulatory role for external Mg cations in the responses of neocortical neurones to the transmitter substances, acetylcholine and GABA, can be inferred from these investigations which simulate hypomagnesemia. The dose-dependent depression of GABA actions by low extracellular [Mg2+] additionally provides a plausible mechanism that may contribute to the neuronal hyperexcitability that is observed during conditions of hypomagnesemia.
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PMID:Effects of hypomagnesia on transmitter actions in neocortical slices. 198 29

Although depression is common among alcoholics, its determinants are poorly understood. Among 339 alcoholics, 111 (33%) had a history of major depression. Depressed, compared with never-depressed alcoholics, had a higher daily alcohol intake, more lifetime diagnoses of other anxiety and affective disorders and drug abuse, more had attempted suicide, and more reported alcoholism in both parents. Depressed alcoholics also had significantly lower cerebrospinal fluid levels of the dopamine metabolite homovanillic acid and of gamma-aminobutyric acid. Among subgroups of depressed alcoholics, secondary compared with primary depressives were more often divorced, of lower social status, with an earlier onset of alcoholism, and higher Michigan Alcohol Screening Test scores. Secondary depressives also had significantly lower cerebrospinal fluid concentrations of homovanillic acid than never depressed alcoholics. These results suggest that certain psychosocial variables, alcohol consumption, and neurochemical variables may be specifically associated with depression in alcoholics.
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PMID:Depression among alcoholics. Relationship to clinical and cerebrospinal fluid variables. 202 Dec 95

We assessed the role of gamma-aminobutyric acid (GABA) as a potential causative agent of hypoxic respiratory depression by monitoring the response of the phrenic neurogram to systemic infusion of the GABA antagonist bicuculline (0.01 mg.kg-1.min-1) under control conditions and during isocapnic brain hypoxia produced by CO inhalation in separate groups of anesthetized, glomectomized, vagotomized, paralyzed, and ventilated cats with blood pressure held constant. The maximum effect of bicuculline in subseizure doses in control cats was to increase minute phrenic activity to 151 +/- 14% of preinfusion values. Infusion was continued until seizure activity was seen in the electroencephalogram. A 53% decrease of arterial O2 content resulted in a marked reduction of both peak phrenic amplitude and phrenic firing frequency to 16 and 64% of control values, respectively. Infusion of bicuculline while the level of hypoxia was maintained constant restored both peak phrenic amplitude and phrenic firing frequency to prehypoxic levels. The maximum effect of bicuculline was to increase minute phrenic activity to 123 +/- 13% of the prehypoxic value. These results suggest that although GABA has only a modest role in determining the output of the control phrenic neurogram, a significant portion of the phrenic depression that occurs during hypoxia can be attributed to inhibition of respiratory neurons by GABA.
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PMID:GABA antagonism reverses hypoxic respiratory depression in the cat. 212 85

Cocaine potently inhibits the spontaneous activity of dorsal raphe serotonin (5-hydroxytryptamine [5-HT] neurons which possess impulse-modulating receptors of the 5-HT1A subtype. In an investigation of the neuropharmacologic mechanisms underlying this electrophysiologic effect, we have compared cocaine with structurally and functionally similar compounds, attempted to reverse cocaine-induced suppression of 5-HT dorsal raphe nucleus (DRN) neuronal activity, and assessed the effects of 5-HT depletion on the response to cocaine. Extracellular recordings in chloral hydrate-anesthetized rats were obtained using single-unit recording techniques; drugs were infused intravenously IV) in a cumulative dose manner. The active isomer (-)-cocaine (ID50 = 0.5 +/- 0.15 mg/kg) and the phenyltropane analogue WIN 35428 (ID50 = 0.17 +/- 0.03 mg/kg) that share the ability of cocaine to block monoamine uptake also inhibit impulse activity in 5-HT neurons. In contrast, the inactive isomers (+)-cocaine, (+)-pseudococaine and the metabolite benzoylecgonine do not exhibit the same range of potency (maximal 20% to 30% inhibition at a cumulative dose of 8 to 16 mg/kg). A selective inhibitor of uptake for 5-HT (fluoxetine; ID50 = 1.8 +/- 0.5 mg/kg), but not norepinephrine (desipramine) or dopamine (GBR 12909), mimicked cocaine, as did the monoamine releaser amphetamine (ID50 = 2.86 +/- 0.46 mg/kg). The putative 5-HT1A autoreceptor antagonist spiperone reversed the cocaine-induced depression of firing rate in 64% of 5-HT neurons tested whereas receptor antagonists for dopamine D2 (haloperidol), 5-HT2 (ketanserin), gamma-aminobutyric acid (picrotoxin) and 5-HT1/beta-adrenergic (propranolol) were ineffective. Following treatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (100 mg/kg/day of the base for 3 days), impulse depression induced by cocaine was significantly attenuated as compared to control, which suggests that the effects of cocaine may be dependent on endogenous 5-HT stores. In summary, these findings support the hypothesis that the inhibitory effects of cocaine on 5-HT DRN neurons are mediated by increased 5-HT available for interaction with 5-HT1A impulse-regulating autoreceptors in the DRN, as a consequence of cocaine-induced blockade of 5-HT reuptake processes. Further studies are required to clarify the relative contribution of cocaine-5-HT interactions to the behavioral and physiologic effects of this psychostimulant.
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PMID:The interaction of cocaine with serotonin dorsal raphe neurons. Single-unit extracellular recording studies. 213 98

1. The phosphono-analogues of gamma-aminobutyric acid (GABA), 4-amino-butylphosphonic acid (4-ABPA), 3-amino-2-(4-chlorophenyl)-propylphosphonic acid (phaclofen) and 3-amino-2-cyclohexylpropyl-phosphonic acid, each antagonized the GABA- and baclofen-induced GABAB-receptor-mediated depression of twitch responses to transmural stimulation in the guinea-pig isolated ileum, in a concentration-dependent, reversible and surmountable manner (apparent pA2 = 4.0 +/- 0.1, 4 +/- 0.2 and 3.7 +/- 0.2 respectively, compared with 3.9 +/- 0.1 for delta-aminovaleric acid). No such activity was found in a variety of related analogues. 2. By contrast, 3-amino-propylphosphonic acid (3-APPA) behaved as a partial agonist, itself partly depressing ileal twitch contractions in a manner sensitive to 4-ABPA and phaclofen, as well as antagonizing the depression of the ileal twitch by GABA and baclofen (apparent pA2 = 4.0 +/- 0.2). 3. Both 4-ABPA and phaclofen also antagonized the baclofen-induced depression of the twitch in the guinea-pig isolated vas deferens (apparent pA2 = 4.0 +/- 0.1 for each), whilst 3-APPA behaved as a partial agonist, slightly depressing the vas twitch, and antagonised the baclofen-induced depression of the twitch (apparent pA2 = 3.9 +/- 0.1). 4. None of these phosphono-analogues exhibited any action at ileal GABAA-receptors, nor influenced the ileal twitch depression with morphine, adenosine or noradrenaline, suggesting their selectivity as antagonists at GABAB-receptors.
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PMID:Antagonism of GABAB-receptor-mediated responses in the guinea-pig isolated ileum and vas deferens by phosphono-analogues of GABA. 215 79

1. The effect of milacemide, a glycine percursor known to increase gamma-aminobutyric acid (GABA) and glycine content in the brain, and to have anticonvulsant properties, was tested by ionophoresis on 247 neurones situated in the cerebral cortex and in deeper structures of cats and rats anaesthetized with urethane. 2. Virtually all the neurones, either firing spontaneously or exogenously driven by the excitatory amino acids, glutamate, N-methyl-D-aspartate (NMDA), kainate and quisqualate or by acetylcholine, were reversibly depressed in a dose-dependent fashion. The same depressant effect was observed in animals pretreated with the monoamine oxidase B inhibitor (IMAO-B) deprenyl which is known to reduce milacemide metabolism into glycinamide and glycine. Intravenous administration of milacemide (10 to 100 mg kg-1) also depressed the firing induced by glutamate, NMDA and acetylcholine. 3. When compared to GABA, milacemide was a weaker depressant. However, its effect could still be observed in the presence of the reversible GABAA antagonist, SR 95531, and thus milacemide is unlikely to act through GABA receptors. In addition, on cells unaffected by glycine, milacemide also had a depressant effect, and on cells inhibited by glycine, it was still capable of depressing cell firing during reversible blockade by strychnine of the glycine inhibitory action; thus milacemide is unlikely to act through glycine receptors. Simultaneous release of milacemide and GABA or of milacemide and glycine, did not show potentiation of the inhibitory amino acid action. However, the depressant effect of milacemide was additive with that of GABA and glycine. 4. No consistent depression of glutamate-induced firing was obtained by ionophoresis of glycinamide, the first metabolite of milacemide. 5. It is concluded that milacemide by itself is a depressant agent and that its depressant effect does not necessarily require its metabolism into glycine, or its stimulator effect on the production of GABA.
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PMID:Microionophoretic study with milacemide, a glycine precursor, on mammalian central nervous system cells. 219 64

Plasma levels of gamma-aminobutyric acid (GABA) were determined in 68 healthy controls and in 133 patients with mood disorder. Plasma GABA levels were significantly lower in the patients with mood disorder compared to controls. Levels of plasma GABA were similar among diagnostic groups (primary unipolar depression, bipolar depression, mania, and secondary depression). No differences in plasma GABA were found in patients classified according to family history, nor were any correlations found between plasma GABA levels and severity of depression as determined by the 17-item Hamilton Rating Scale for Depression. These findings support the notion that low plasma GABA may represent a biological marker for mood disorder.
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PMID:Plasma GABA in mood disorders. 223 51

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.
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PMID:Chronic intrathecal baclofen administration for control of severe spasticity. 230 74

Tetanic mossy fiber stimulation transiently reduced recurrent inhibition in the rat dentate gyrus. The post-tetanic depression of inhibition was maximal 200 ms after the tetanus and typically lasted for about 2 s. Phaclofen, a selective gamma-aminobutyric acid-B (GABAB) receptor antagonist, significantly increased the post-tetanic level of inhibition. These results suggest that GABAB receptor activation is important for the development of post tetanic disinhibition. We suggest that GABA released during repetitive firing acts on GABAB receptors on inhibitory interneurons to suppress recurrent inhibition.
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PMID:Phaclofen antagonizes post-tetanic disinhibition in the rat dentate gyrus. 232 80

The sensitivity of neurons of the deep cerebellar nuclei to iontophoretic application of taurine (TAU) and gamma-aminobutyric acid (GABA) has been studied in vivo in rats. Both TAU and GABA produced a dose-dependent depression of the firing rate. Both the inhibitory actions of TAU and GABA were antagonized by bicuculline (BIC) and picrotoxin (PIC) but not by strychnine (STRY) meaning that TAU had a 'GABA-like' effect in the deep cerebellar nuclei. Simultaneous application of TAU and GABA induced not an additive but a synergistic inhibitory effect on the discharge of the neurons of the interposed and dentate nuclei. These results indicate the involvement of TAU in the inhibitory processes acting on neurons of the deep cerebellar nuclei.
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PMID:Taurine in deep cerebellar nuclei of the rat. In vivo comparison to GABA inhibitory effect. 235 22


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