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)

The effects of ammonium acetate or chloride, perfused through the lateral ventricle, were studied on the hippocampal formation of the rat. During perfusion with ammonia, the population spikes, evoked by stimuli delivered to the fimbria, were first increased and then reduced. On the other hand, the late positive wave gradually decreased throughout the application of ammonia. The inhibition, studied by the paired-pulse test, was found to be reduced when the population spike was transiently enhanced, indicating that disinhibition could be responsible for the enhancement of synaptically evoked responses. Neither antidromically evoked population spikes nor the typical effects of iontophoretically applied glutamate, aspartate or gamma-aminobutyrate were changed by ammonia. These findings can be accounted for by a single action of ammonia, a depression of excitatory synaptic transmission, the excitatory synapses on inhibitory interneurons being more readily depressed than those on the pyramidal cells. Both effects, early hyperexcitability and late depression, are probably due to a reduction in the release of the excitatory neurotransmitter, glutamate and/or aspartate. We tentatively suggest that these mechanisms are responsible for some of the symptoms observed during the development of hyperammonemic encephalopathies.
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PMID:Effects of ammonium salts on synaptic transmission to hippocampal CA1 and CA3 pyramidal cells in vivo. 285 53

In order to define the modulatory role played by gamma-aminobutyric acid (GABA) in corticopetal cholinergic projections, the effect of this amino acid and related drugs on gross behaviour, the EEG and the release of acetylcholine (ACh) from the cerebral cortex in freely moving guinea-pigs was studied. gamma Aminobutyric acid, injected intracerebroventricularly (20-50 mumol) induced a three-phase picture: first (5-15 min) behavioural activation and increased release of ACh, then (30-90 min) depression, EEG synchronization and reduced release of ACh, and finally "rebound" stimulation. Ethanolamine-O-sulphate (EOS) injected intraventricularly (28 mumol/kg) or intraperitoneally (14 mmol/kg) reproduced the first two phases of the effects of GABA (i.e. stimulation followed by inhibition), while diazepam (0.7 and 3.5 mumol/kg, i.p.) and flurazepam (32 mumol/kg, i.p.) caused, at first, only depression. Muscimol and 4,5,6,7-tetrahydroisoxazolo(4,5-c)pyridine-3-ol (THIP) injected intraventricularly (in the nmol range) or intraperitoneally (in the mumol range) produced behavioural activation and increased release of ACh; the depressant signs appeared only after very large, toxic doses. Picrotoxin and bicuculline, at sub-convulsive doses, reduced the symptomatology caused by GABA and antagonized the sedation produced by diazepam. Methysergide (8-16 mumol/kg, i.p.) prevented the behavioural activation and the increased release of ACh by GABA, unmasked the depression due to subthreshold doses of diazepam (i.c.v., 7-70 nmol) and reversed the stimulation induced by muscimol into sedation and reduced the outflow of ACh. Pretreatment with 5,7-HT also dampened and shortened the stimulation by muscimol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The modulation of cortical acetylcholine release by GABA, GABA-like drugs and benzodiazepines in freely moving guinea-pigs. 286 May 90

The action of some cholinergic drugs has been studied on the field potentials evoked by orthodromic stimulation of the lateral olfactory tract (LOT) in guinea-pig olfactory cortex slices maintained in vitro. A reversible depression of the electrically evoked surface-negative field potential (N-wave) was seen following superfusion of muscarine (10-200 microM) or mixed-agonist choline esters but not nicotinic agonists. This depression was blocked by atropine and pirenzepine, but not d-tubocurarine or by antagonists active at gamma-aminobutyric acid or adenosine receptors. Little effect of muscarinic agonists was observed on the compound action potential recorded from the LOT, or on pial surface DC potential. A possible presynaptic site of action of muscarinic agonists in the olfactory cortex is discussed.
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PMID:Muscarinic depression of evoked surface-negative field potentials recorded from guinea-pig olfactory cortex in vitro. 286 10

Structure-activity of primary afferent depolarising action (PAD) mediated by gamma-aminobutyrate (GABA) analogues suggests a difference between subsynaptic receptors located at fibre terminations within the dorsal horn and axonal receptors which are distributed throughout non-synaptic regions. The interaction of the bicuculline-sensitive GABA receptor (GABA A) ionophore complex with barbiturates and benzodiazepines suggests that at least three binding sites are required to explain the independent GABA-mimetic, GABA-potentiating and picrotoxin-reversing effects of such agents. Difficulties with explanation of the depressant effects of baclofen on spinal transmission, in terms of the bicuculline-resistant GABA (GABA B) receptor hypothesis, are mentioned. Glutamate-induced PAD of low threshold afferents is mediated indirectly through release of potassium. However, such terminals possess receptors (possibly autoreceptors for L-glutamate), activated by (+)2-amino-4-phosphonobutyrate, which cause depression of transmitter release. Primary afferent C-fibres possess receptors which are selectively activated by kainate and which mediate picrotoxin-resistant PAD. Such receptors may be involved in the presynaptic conditioning of C-fibre transmitter release. The peripheral terminals of vestibular primary afferents, in amphibia, possess excitatory amino acid receptors which are probably activated by the transmitter released from hair cells.
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PMID:Pharmacology of amino acid receptors on vertebrate primary afferent nerve fibres. 286 69

Interactions between the benzodiazepines (BZs) chlordiazepoxide (CDP) and midazolam (MDZ), the BZ antagonist R0 15-1788, the inverse BZ receptor agonists CGS 8216 and FG 7142, gamma-aminobutyrate (GABA), serotonin (5-HT), the 5-HT2 antagonist methysergide and the putative 5-HT agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) were investigated using peripheral and intra-amygdaloid treatments. A multiple schedule consisting of rewarded, nonrewarded (Time out: TO) and conflict periods was used to compare in parallel effects on successive discrimination between rewarded and nonrewarded periods and punished responding. The three components were presented in both a fixed order (Experiment 1) and a random order (Experiments 2 and 3). Intra-amygdaloid treatments with GABA and the BZs selectively increased rates of punished responding. CDP given systemically, on the other hand, increased both TO and conflict rates, suggesting an additional impairment of discrimination, which was more marked in the random than the fixed order condition. R0 15-1788, CGS 8216 and FG 7142 given by both routes counteracted the anti-conflict effects of CDP given centrally or systemically. However increases in TO rates induced by IP CDP were antagonized only by IP treatments with these compounds. The two inverse agonists, but not R0 15-1788, also counteracted increases in punished responding which were found after intra-amygdaloid GABA infusions. In Experiments 2 and 3 where baseline rates of pressing in Conflict periods were sufficiently high to detect decreases, CGS 8216 and FG 7142 reduced responding below control level, suggesting a specific anxiogenic activity. Evidence for effects of R0 15-1788 by itself was inconclusive. 5-HT injected into the amygdala also reduced punished responding below control level, whereas methysergide increased it with both central and peripheral treatment. Effects of 8-OH-DPAT varied according to route of administration. With IP treatment Conflict rates were increased, but after amygdaloid infusion both TO and Conflict rates were marginally reduced below control level, with a more consistent depression of punished responding. These results provide evidence that effects of BZs on punished responding are mediated by a GABAergic system which includes the lateral/basolateral amygdala, but which does not participate in BZ-induced disruption of discrimination. They also indicate that the antagonistic effects of CGS 8216 and FG 7142 involve a decrease in GABA transmission, and that these compounds may also be anxiogenic.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence that the amygdala is involved in benzodiazepine and serotonergic effects on punished responding but not on discrimination. 288 53

The authors studied the effect of two biologically active substances (gamma-aminobutyric acid-GABA, pentobarbital-PB) and a physical factor (temperature-T) on the direct response of parallel fibres of the isolated frog cerebellum to electrical stimulation in vitro. The extrasynaptic action of GABA and PB during superfusion (10(-6), 10(-5), 10(-4) and 10(-3) mol.l-1) significantly reduced the amplitude of the response of parallel fibres. Superfusion with picrotoxin (10(-6) mol.l-1) only partly blocked the effect of GABA (10(-3) mol.l-1), although it abolished the effect of PB (10(-3) mol.l-1). Cooling the cerebellum from the control temperature (T = 16 degrees C) to T = 13 and 10 degrees C significantly augmented the amplitude of the responses, while raising it to 19 and 22 degrees C significantly reduced their amplitude. At T = 13 degrees C, depression of direct responses was significant only in superfusion with GABA (10(-6) and 10(-3) mol.l-1) and not in superfusion with PB (10(-6) and 10(3-) mol.l-1). The results with picrotoxin (PTX) applications, indicated that the extrasynaptic action of GABA and PB took effect by partly different mechanisms. That would account for the difference in the effect of GABA and PB in conjunction with the physical factor.
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PMID:The extrasynaptic effect of gamma-aminobutyric acid and pentobarbital and the influence of temperature on the response of parallel fibres of the frog cerebellum in vitro. 297 8

GABAB receptors are a subclass of receptors for gamma-amino-n-butyric acid (GABA) that are also activated by the antispastic drug beta-p-chlorophenyl-GABA (baclofen). One effect of baclofen is to inhibit excitatory transmission from CA3 to CA1 hippocampal pyramidal cells. To identify the ionic mechanism of GABAB-receptor-mediated depression, we have studied the effect of baclofen and GABA on ionic currents in voltage-clamped CA3 pyramidal cell somata in rat hippocampal slice cultures. Baclofen (10 microM) induced an inwardly rectifying outward current that reversed at -74 +/- 4.3 mV (mean +/- SD). This appeared to be a K+ current since (i) its reversal potential showed the expected shift when extracellular K+ concentration was changed and (ii) it was blocked by external Ba2+ or internal Cs+. The action of baclofen was closely imitated by GABA after the GABAA-mediated Cl- current had been abolished with pitrazepin (10 microM); under these conditions, GABA (100 microM) also produced an inwardly rectifying, Ba2+-sensitive current with a reversal potential identical to that of the baclofen-induced current. When outward currents were blocked with internal Cs+, the residual inward voltage-dependent Ca2+ current was not changed by baclofen. It is concluded that the primary effect of GABAB-receptor activation in these neurones is to increase K+ permeability rather than to reduce Ca2+ permeability.
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PMID:GABAB-receptor-activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures. 298 51

We have used intracellular recording techniques to study the use-dependence of evoked inhibitory postsynaptic potentials (IPSPs) in rat CA1 hippocampal pyramidal cells. We determined reversal potentials and conductance changes associated with IPSPs and responses to directly applied gamma-aminobutyric acid (GABA). The IPSP depression could be seen after a single conditioning stimulus. This depression appeared to be due primarily to a 50% decrease in IPSP conductance (gIPSP). Trains of stimulating pulses (50 pulses at 5 or 10 Hz) produced more pronounced effects than a single conditioning pulse. Suprathreshold repetitive stimulation of stratum radiatum (SR) produced epileptiform burst firing and greater depression of IPSPs than did alvear (ALV) or subthreshold SR stimulation. During suprathreshold SR stimulation the IPSP was nearly abolished and the membrane potential could become less negative than the resting potential. A masking effect of facilitated depolarizing potentials on IPSPs was unlikely since IPSPs accompanied by little or no depolarizing potential were also depressed by SR trains. The 75% reduction in IPSP conductance found after repetitive stimulation confirmed that an overlapping conductance was not responsible for the depression of the IPSP. The GABA-induced conductance increase was not depressed by identical trains. Trains of stimulation induced depolarizing shifts in equilibrium potentials for the IPSP (EIPSP) and GABA (EGABA) of approximately 10 mV. These shifts were always greater after SR trains than after ALV trains. Simultaneous recordings of membrane potential and extracellular potassium concentration ([K+]o) with K+-sensitive microelectrodes revealed a direct correlation between the two during a stimulus train. Membrane potential depolarized as much as 18 mV from the peak of the IPSP and [K+]o could increase to a maximum of 10 mM during some trains. A depressant effect (of approximately 50%) of K+ on IPSPs was demonstrated by brief pressure ejection of K+ near the soma. We conclude that repetitive stimulation depresses gIPSP and shifts EIPSP in the depolarizing direction. Whereas gIPSP began to decline after a single conditioning pulse, the additional depression of IPSPs produced by stimulus trains was due in large part to shifts in EIPSP. Depression of gIPSP was not due to desensitization or block of ionic conductances, since gGABA was not reduced. The EIPSP may change as a result of increases in [K+]o.
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PMID:Use-dependent depression of IPSPs in rat hippocampal pyramidal cells in vitro. 298 52

Pentobarbitone depresses synaptic excitation in the guinea-pig olfactory cortex slice in vitro. A study has been made to elucidate the possible role of gamma-aminobutyric acid (GABA) in this depression by testing pentobarbitone in the presence of high concentrations of the GABA blockers, i.e. picrotoxin or bicuculline. These blockers reduced the action of pentobarbitone; the dose-depression curve for pentobarbitone was shifted to the right by a factor of 2.3. It is concluded that pentobarbitone has a bimodal action, one action via GABA and another unrelated to GABA or Cl- conductances.
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PMID:gamma-Aminobutyric acid partly mediates the pentobarbitone depression of synaptic excitation in the guinea-pig olfactory cortex in vitro. 298 34

The action of different classes of clinically effective antidepressants and electroshock on gamma-aminobutyric acid (GABA) B recognition sites in the frontal cortex was compared to that of other psychotropic agents. After either prolonged (6-18 days) s.c. infusion via osmotic minipumps or repeated i.p. injections of different antidepressants, or a series of electroshocks, treatment was halted and 72 hr later the animals were sacrificed, the brain was dissected and frozen. All major antidepressants (desipramine, amitryptyline or maprotiline), several newer compounds with reported antidepressant activity (viloxazine, zimelidine, fluoxetine, citalopram, progabide, fengabine, sodium valproate, mianserin, trazodone or nomifensine) as well as pargyline and repeated electroshocks, up-regulated GABA B binding in the rat frontal cortex but not hippocampus. This appeared to be a maximum binding effect, but in some instance the kinetics were more complex. Reserpine, diphenylhydantoin and phenobarbital down-regulated GABA B binding in the frontal cortex, whereas this was unaltered by haloperidol, chlorpromazine or diazepam administration. Desipramine up-regulated GABA B binding in a dose- and time-dependent manner (minimum effective dose, 1.25 mg/kg/day s.c. for 18 days; onset of action, 6 days at 5 mg/kg/day s.c.). Together with the rather sparse data in the literature on GABA in depression and antidepressant drug action, these findings support a common GABAergic mechanism of action of antidepressant drugs and electroshock, mediated via GABA B synapses.
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PMID:Upregulation of gamma-aminobutyric acid (GABA) B binding sites in rat frontal cortex: a common action of repeated administration of different classes of antidepressants and electroshock. 299 46


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