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

1. The responses of spontaneously active single neurones in the substantia nigra and overlying mesencephalic reticular formation have been analysed during the electrical stimulation of the ipsilateral caudate nucleus. Experiments were performed in rats anaesthetized with urethane or pentobarbitone. All recordings were made extracellularly with multi-barrelled glass micropipettes which were also used to test neuronal responsiveness to electrophoretically administered substances. The micropipette tip position was marked and the distribution of neurones studied has been analysed. 2. Single shock stimulation of the caudate nucleus inhibited neuronal activity in the substantia nigra (270/320 cells: mean latency 5-4 msec) and in the mesencephalic reticular formation (62/72 cells: mean latency 16-6 msec). However, these effects were often accompanied by periods of excitation. In pentobarbitone anaesthetized animals the latency and duration of these substantia nigra inhibitions was increased. 3. Compared with the zona reticulata, fewer neurones in the zona compacta of the substantia nigra responded to caudate stimulation in both urethane or pentobarbitone anaesthetized animals. 4. The activity of most cells was depressed by electrophoretically administered GABA or glycine and increased by acetylcholine or glutamate. Neurones of the mesencephalic reticular formation were less sensitive to GABA and glycine than substantia nigra neurones. Within the substantia nigra, both zona compacta and zona reticulata neurones were more sensitive to GABA than to glycine. Over-all, glutamate was a more potent excitant than acetylcholine (ACh). 5. Electrophoretic bicuculline methochloride (BMC) consistently reduced GABA but not glycine depression of substantia nigra neurones. Approximately twice as much BMC was required to reduce the endogenous inhibition of the same substantia nigra neurones and the amplitude of concomitantly evoked positive field potential as was required to abolish exogenous GABA responses. Some evoked substantia nigra inhibitions were resistant to BMC. 6. Electrophoretic strychnine consistently reduced glycine but not GABA depression of substantia nigra neurones, and did not modify caudate evoked inhibition of these neurones or the accompanying field potential. 7. The results support the concept of a slowly conducting caudato-nigral pathway which has both facilitatory and inhibitory components. The inhibitory pathway uses GABA as the neurotransmitter. The identity of the possible excitatory transmitter is unknown. The monosynaptic nature of this pathway is uncertain and the possible contribution of other bicuculline insensitive nigral inhibitory processes is discussed.
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PMID:Caudate stimulation and substantia nigra activity in the rat. 0 37

The effects of diazepam, flunitrazepam, phenobarbitone and baclofen on excitatory as well as on pre- and postsynaptic inhibitory processes in the cuneate nucleus were studied in decerebrate cats. Afferent presynaptic inhibition in the cuneate nucleus, evoked by volleys in the median nerve, and assessed by the size of the positive cuneate surface potential (P wave), the dorsal column reflex (DCR), and the increased excitability of primary afferent terminals of the ulnar nerve, was markedly enhanced by diazepam (0.1-3.0 mg/kh i.v.) and flunitrazepam (0.01-0.3 mg/kg i.v.), slightly enhanced by lower doses of phenobarbitone (3-20 mg/kg i.v.), but depressed by baclofen (1-10 mg/kg i.v.). Diazepam, flunitrazepam and phenobarbitone also increased postsynaptic inhibition in the cuneate nucleus which was measured by the decrease after conditioning volleys in the median nerve of the short-latency lemniscal response to cuneate stimulation. The GABA receptor blocking agent, picrotoxin, antagonized the effects of diazepam on pre- and postsynaptic inhibition in a surmountable way. After thiosemicarbazide (TSC), an inhibitor of GABA synthesis, both pre- and postsynaptic inhibition were greatly reduced and the augmenting effect of diazepam on both types of inhibition was nearly abolished. Aminooxyacetic acid (AOAA), an inhibitor of GABA degradation, slightly enhanced pre- and postsynaptic inhibition; the effects of diazepam were unaffected by AOAA. Diazepam, flunitrazepam and phenobarbitone did not alter the resting excitability of primary afferent endings or of cuneo-thalamic relay (CTR) cells in the cuneate nucleus. After higher doses (30 mg/kg i.v.) of phenobarbitone pre- and postsynaptic inhibition, which were enhanced by 10 mg/kg of this drug, tended to return to pre-drug values or below. Phenobarbitone, in contrast to benzodiazepines, also depressed in a dose-dependent way the N wave, which is an index of the orthodromic excitation of the CTR cells. Baclofen strongly depressed the cuneate N wave, decreased the excitability of CTR cells, reduced pre- and postsynaptic inhibition, but had no effect on the resting excitability of primary afferent endings. Our findings suggest the following modes of action of the above mentioned drugs: 1. benzodiazepines enhance selectively the GABA-mediated pre- and postsynaptic inhibition in the cuneate nucleus; 2. phenobarbitone slightly enhances pre- and postsynaptic inhibition only in a narrow dose range, and in addition reduces the excitatory processes in the cuneate nucleus; 3. baclofen seems to depress the excitation of cuneate relay cells and interneurones postsynaptically; the depression of relay cells is probably nonspecific.
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PMID:Effects of two benzodiazepines, phenobarbitone, and baclofen on synaptic transmission in the cat cuneate nucleus. 1 11

A comparative study of the effect of some benzodiazepine deprivatives (chlonazepam, lorazepam, diazepam, and medazepam) on the recovery cycles of the interzonal response was carried out on unanesthetized curare-immobilized cats. These drugs proved to selectively inhibit the testing potential within the range of 20 to 100 msec. between the conditioning and the testing stimuli. This indicates that potentiation of GABA-ergic inhibition in the cerebral cortex. The threshold doses of the drugs inducing the depression of the test response and of ED50, preventing the development of convulsions, caused by GABA deficiency or by GABA-ergic receptor block, were compared; a correlation between the mentioned effects was demonstrated. The significance of GABA-positive effect of benzodiazepines in the mechanism of their anticonvulsive activity is suggested.
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PMID:[Inhibitory processes in the cerebral cortex and the anticonvulsive action of benzodiazepine derivatives]. 2 Oct 7

Sedative drugs are intended to cause various degrees of drowsiness. Animal experiments indicate that barbiturates induce these effects primarily by depression of the reticular activating system in the rostral brainstem. This in turn potentiates the thalamic recruiting system, thereby inducing 'barbiturate bursts' in the EEG. Anxiolytic drugs are intended to reduce anxiety or tension at doses which do not cause sedation or sleep. Propanediols may depress deactivating centers in the caudal brainstem, thereby releasing the activating centers in the rostral brainstem and depressing the thalamic recruiting response. These drugs may also act on the amygdala. Benzodiazepines have depressant effects on the amydala or hippocampus. These effects may release the reticular formation from inhibition. Enhanced activity of the activating and deactivating centers, to a different extent in different animals, would produce restlessness in some animals and sedation in others, accompanied by a mixture of fast and slow waves in the EEG. Sedative and anxiolytic agents also have central relaxant effects. The barbiturates act directly on the spinal cord, depressing both monosynaptic and polysynaptic reflexes. Propanediols and benzodiazepines act primarily on the descending facilitatory influence of the brainstem. Reduction of this influence depresses spinal polysynaptic but not monosynaptic reflexes. Biochemical studies suggest that barbiturates may act by antagonizing synaptic excitation induced by glutamate. Benzodiazepines may act by enhancing presynaptic inhibition mediated by GABA. The mechanism of action of propanediols is unknown.
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PMID:Neuropharmacology of sedatives and anxiolytics. 3 29

Rats were maintained on ad lib food and a forced-intake regimen of ehtanol for up to 270 days. The ethanol treatment induced alterations in the metabolism of central catecholamines seen as increased endogenous concentrations of dopamine concomitantly with decreased concentrations of noradrenaline in the limbic forebrain. The synthesis of catecholamines, measured as the accumulation of dopa following inhibition of aromatic amino acid decarboxylase, was unchanged during chronic ethanol treatment. Local application of dopamine into the nucleus accumbens caused a greater increase in locomotor activity in chronic ethanol rats than in controls thus indicating that chronic ethanol treatment increased the sensitivity at or beyond central dopamine receptors. This phenomenon of functional dopamine receptor supersensitivity was first observed after 5 months of ethanol treatment and lasted for about 4 weeks after cessation of the ethanol treatment. The sensitivity of noradrenergic and cholinergic receptor mechanisms appeared to be unchanged after chronic exposure to ethanol. The effect of the GABAergic drug, gamma-butyrolactone (GBL) on the accumulation of dopa after inhibition of aromatic amino acid decarboxylase was studied in chronic ethanol rats. The enhancement of the dopa formation in dopaminergic neurons induced by GBL was markedly attenuated after chronic ethanol treatment. The gross behavioural depression by GBL was also weakened. This may indicate that chronic ethanol treatment causes subsensitivity of GABA receptors.
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PMID:The effect of chronic ethanol administration on central neurotransmitter mechanisms. 4 85

1. Bath-application of L-glutamate to crayfish opener muscle causes depolarization and resistance changes which both increase with falling temperature. At temperatures above 15 degrees C there is usually a resistance increase, at lower temperatures the resistance is decreased. 2. Meso-gamma . gamma'-diaminosuberic acid-dihydrochloride (meso-di-GABA) and dl-diamino-nonanedicarboxylic acid dihydrochloride (C-9) were newly synthesized as potential glutamate blockers. 3. Meso-di-GABA (10(-4) to 10(-3)M) usually caused a significant increase (15 degrees C) or decrease (7 degrees C) of membrane resistance and slight depolarization. Excitatory junction potentials (ejps) were reversibly depressed or blocked while the effects of glutamate were potentiated. The depression or block of neuromuscular transmission was not prevented by picrotoxin or by concanavaline A. 4. C-9 (3 x 10(-4) M) depressed or blocked the effect of applied glutamate with little or no effect on ejps. 5. The results are best explained by assuming that bath-applied glutamate acts mainly on extrasynaptic receptors. Meso-di-GABA is assumed to block synaptic receptors and to activate non-synaptic receptors while C-9 seems to act mainly as a blocker of glutamate action on non-synaptic receptors.
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PMID:Is glutamate the transmitter of crustacean motoneurons? 4 27

Previous studies had suggested that the epileptic bursts of feline generalized penicillin epilepsy represent the response of hyperexcitable cortex to thalamocortical volleys normally evoking spindles. If this were the case, it should be possible to convert the epileptic bursts of generalized penicillin epilepsy into spindles by decreasing the excitability of cortical neurons. In cats exhibiting the EEG signs of feline generalized penicillin epilepsy cortical excitability was decreased by hypoxia, by the topical application to the cortex of KCl (inducing spreading depression), barbiturates, GABA, AMP or noradrenaline. During generalized penicillin epilepsy, hypoxia and KCl-induced spreading depression abolished epileptic bursts which were replaced by spindles. When spindles and epileptic complexes occurring in the same animal were compared, a direct correlation between the frequencies of these two rhythms could be demonstrated, that of the epileptic complexes being about half that of the spindle waves. These observations support the hypothesis that the epileptic bursts of feline generalized penicillin epilepsy are induced by thalamocortical volleys normally involved in spindle genesis. Topical cortical applications of barbiturates, GABA, AMP and noradrenaline reduced or inverted the negative spikes of the spike and wave complexes, while augmenting the negative slow waves, or revealing them clearly in instances in which they had been poorly developed. This effect is interpreted as being due to a selective inactivation of the superficial cortical layers. That topical cortical application of barbiturates, GABA, AMP and noradrenaline was capable of transforming into typical spike and wave complex epileptic bursts, which had not previously conformed to this pattern, indicates that the intracortical electrophysiological events of typical and atypical epileptic bursts in feline generalized penicillin epilepsy are fundamentally the same and reflect an alternation between excitatory and inhibitory sequences.
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PMID:Effects of changes in cortical excitability upon the epileptic bursts in generalized penicillin epilepsy of the cat. 8 21

Chronic ammonia toxicity in experimental mice was induced by exposing them for 2 and 5 days to 5 % (v/v) ammonia solution. The enzymes concerned with glutamate metabolism (aspartate-, alanine- and tyrosine aminotransferases, glutamate dehydrogenase and glutamine synthetase) and (Na+ + K+)-ATPase were estimated in the three regions of brain (cerebellum, cerebral cortex and brain stem) and in liver. Glutamate, aspartate, alanine, glutamine and GABA, RNA and protein were also estimated in the three regions of brain and liver. A significant rise in the activity of (Na+ + K+)-ATPase in all the three regions of brain along with a fall in the activity of alanine aminotransferase was noticed. Changes in the activities of other enzymes were also observed. A significant increase in alanine and a decrease in glutamic acid was observed while no change was observed in the content of other amino acids belonging to the glutamate family. As a result of this, changes in the ratios of glutamate/glutamine and glutamate + aspartate/GABA was observed. The results indicated that the brain was in a state of more depression and less of excitation. Under these conditions the liver tissue was showing a profound rise in the activity of the enzymes of glutamate metabolism. The results are further discussed.
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PMID:Chronic metabolic effects of ammonia in mouse brain. 9 19

The effect of manipulation of GABA mechanisms in the region of the nucleus accumbens on dopamine-dependent locomotor hyperactivity in the rat has been studied. Two models of hyperactivity were used: (1) the injection of dopamine into the region of the nucleus accumbens in nialamide-pretreated animals and (2) the systemic administration of d-amphetamine. Both GABA and the GABA agonist 3-aminopropane sulphonic acid (3-APS) depressed hyperactivity in a dose-related manner. High concentrations of GABA (greater than 100 micrograms) were required to produce a significant effect and the response was short-lived possibly reflecting the efficient GABA inactivating mechanisms. 3-APS proved to be approximately 10 times more potent as compared to GABA in the dopamine-accumbens hyperactivity model. Conversely GABA receptor antagonism with low doses of either picrotoxin or bicuculline enhanced the mild locomotor response induced by a low dose of dopamine injected into the nucleus accumbens. However such results were difficult to evaluate fairly as higher doses of the GABA antagonists resulted in varying degrees of generalized seizures. Blockade of GABA uptake systems with cis-1, 3-aminocyclohexane carboxylic acid (ACHC), nipecotic acid or beta-alanine within the region of the nucleus accumbens produced dose-related depression of dopamine-dependent hyperactivity in both models. GABA uptake blockade (nipecotic acid) significantly enhanced the GABA-mediated depression of hyperactivity induced by bilateral injection of dopamine into the nucleus accumbens. The results demonstrate an inhibitory action of GABA and drugs facilitating GABA-ergic transmission on dopamine-dependent hyperactivity in the rat. Although open to criticisms of not being able to distinguish between true GABA effects and the results of non-specific neuronal depression the hyperactivity model underlines the potency of the GABA uptake blocking compounds and their possible potential for future clinical use.
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PMID:Dopamine-dependent hyperactivity in the rat following manipulation of GABA mechanisms in the region of the nucleus accumbens. 11 17

The mechanism of stimulatory action of thyrotropin-releasing hormone (TRH) on spontaneous motor activity was investigated in rats. TRH produced a significant hyperactivity with intraperitoneal administration of 20 mg/kg or bilateral injection of 10 micrograms into the nucleus accumbens septi (NAS). Following bilateral injection of 6-hydroxydopamine into the mesolimbic dopamine (DA) pathway, the hyperactivity induced by TRH was not altered, whereas the response to apomorphine given intraperitoneally or DA injected into the NAS was clearly enhanced. The TRH-induced hyperactivity was remarkably suppressed by alpha-methyltyrosine and in contrast, augmented by pargyline. Systemic injection of aminooxyacetic acid in a dose producing behavioral depression reduced markedly the TRH-induced hyperactivity. Bilateral injection of ethanolamine O-sulphate (100 micrograms) into the NAS produced no behavioral depression per se, but remarkably attenuated the hyperactivity response to TRH or DA (20 micrograms) given intraperitoneally or into the NAS. Both TRH (10(-5) and 10(-4) M) and methamphetamine (10(-6)--10(-4) M increased the spontaneous release of 14C-DA from rat NAS slices. These findings suggest that TRH induces hyperactivity by enhancing DA release from nerve terminals in the NAS without a direct stimulation of the post-synaptic DA recptors. TRH and GABA, independently or via interaction between them, may play a reciprocal regulatory role in the activity of the mesolimbic DA system.
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PMID:Thyrotropin-releasing hormone: hyperactivity and mesolimbic dopamine system in rats. 11 87


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