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

Previous studies describe a depression in potassium-evoked, calcium-dependent transmitter release from guinea pig cerebrocortical synaptosomes in response to compression to 68 ATA with heliox. The study described in this paper was designed to evaluate whether a similar effect could be detected at lower pressures and to determine whether the effect had an abrupt onset with a fixed response or a progressive response varying over a range of pressures. A typical response to potassium-evoked depolarization was observed at all pressures studied. This consisted of an initial rising phase lasting 2 to 3 min followed by a falling phase. There was a pressure-dependent depression in the absolute amount of transmitter released as well as a depression in the rate of release in the first minute following stimulation. The mean depression in gamma-aminobutyric acid release during the first minute was an average of 15% at 19 ATA, 28% at 37 ATA, 38% at 50 ATA, and 54% at 62 ATA when compared to a 1 ATA control.
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PMID:Pressure-dependent changes in the release of GABA by cerebrocortical synaptosomes. 274 Dec 57

Hibernation was induced in hamsters by placing them in a cold room for an extended period of time, after which the hibernating state was confirmed by marked reductions in heart rate, body temperature, and the respiratory rate. The animals were either frozen intact in liquid nitrogen, or aroused and then frozen when body temperature reached 8, 12, 16, 20, 24 or 32 degrees C. A metabolite profile, including glucose-related metabolites, high-energy phosphates, gamma-aminobutyric acid (GABA) and cyclic nucleotides, was determined for both the cerebral cortex and cerebellum. In general, the metabolite changes in the two regions elicited by hypothermia were alike, although some differences were evident. The brains of hibernators were biochemically characterized by (1) a high concentration of energy reserves including glycogen, glucose, adenosine triphosphate, and P-creatine, (2) significantly elevated levels of lactate and GABA, and (3) near depletion of cyclic guanosine monophosphate with only a moderate depression of cyclic adenosine monophosphate. During arousal, the metabolites were restored to near normal values and there was little or no indication that the brain energy metabolism was compromised by the arousal process. The study provides certain insights into the metabolic adaptation of the brain to prolonged periods of profound hypothermia in a hibernating species.
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PMID:Metabolism in the hamster brain during hibernation and arousal. 274 44

We have previously shown that the physiological and behavioral manifestations of emotional stress are produced when drugs impairing gamma-aminobutyric acid (GABA)-mediated synaptic inhibition are injected into the posterior hypothalamic nucleus in rats [Wible, J.H., Jr., F.C. Luft, and J.A. DiMicco. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R680-R687, 1988]. The purpose of this study was to assess further the potential role of GABA receptors in this region in the response to stress using muscimol, a GABAA receptor agonist. In six chronically instrumented conscious rats, air stress after vehicle treatment evoked marked and sustained tachycardia (+130 +/- 14 beats/min at +10 min) accompanied by a less dramatic increase in arterial pressure (+14 +/- 3 mmHg). Microinjection of muscimol (10 ng; 88 pmol) at the same posterior hypothalamic site in which GABA blockade causes cardiovascular changes similar to those seen in stress produced a modest depression of cardiovascular function in unstressed animals (-28 +/- 5 beats/min and -6 +/- 3 mmHg). However, similar treatment with muscimol virtually abolished the stress-induced tachycardia in the same rats (+9 +/- 8 beats/min), while having no significant effect on baroreflex-evoked increases in heart rate caused by intravenous infusion of sodium nitroprusside (4 micrograms). These findings support a role for activation of neurons in the posterior nucleus of the hypothalamus in the generation of stress-induced cardiovascular changes and for control of this mechanism by local GABA receptors.
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PMID:Injection of muscimol into posterior hypothalamus blocks stress-induced tachycardia. 275 Sep 64

The effects of bombesin and related peptides on functionally identified single dorsal horn neurones were studied using iontophoresis and extracellular recording in the anaesthetized and spinalized cat. Bombesin selectively depressed superficial dorsal horn neurones (in laminae I-III). The depression was of spontaneous activity as well as of synaptically elicited responses to natural stimulation of the cutaneous receptive field. Bombesin preferentially depressed neurones that responded to noxious stimulation of the cutaneous receptive field. Naloxone, bicuculline and caffeine failed to block the depression by bombesin, suggesting that the effect of the peptide may be direct and not through the indirect activation of an inhibitory system mediated by opioids, by gamma-aminobutyric acid (GABA) or by purines, respectively. Iontophoretic application of neuromedin B (n = 3) and neuromedin C (GRP-10) (n = 7) induced a similar depression to that observed with bombesin. These results provide physiological evidence that a bombesin-like peptide may play a role in the mediation or the modulation of sensory transmission in the superficial dorsal horn of the spinal cord.
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PMID:Bombesin, neuromedin B and neuromedin C selectively depress superficial dorsal horn neurones in the cat spinal cord. 279 Apr 61

Diazepam-binding inhibitor (DBI) is a neuromodulatory peptide for gamma-aminobutyric acid (GABA) neurotransmission. Cerebrospinal fluid (CSF) levels of DBI have been found to be elevated in depression. CSF levels of the peptide corticotropin-releasing hormone (CRH) have also been found to be elevated in depression. Therefore, we examined for a relationship between DBI and CRH in human CSF. We found significant positive correlations between CSF levels of DBI and CRH in depressed patients, pathological gamblers, and normal controls. These data, along with the elevated CSF levels of DBI in depression, 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:Diazepam-binding inhibitor and corticotropin-releasing hormone in cerebrospinal fluid. 281 71

Intracellular recordings from mammalian spinal motoneurons in vivo show that the type B gamma-aminobutyric acid receptor agonist, L-(-)-baclofen, when administered systemically to pentobarbital-anesthetized or decerebrate unanesthetized cats decreases the amplitude of monosynaptic group Ia excitatory postsynaptic potentials (EPSPs), markedly increases tetanic and posttetanic potentiation, and reduces or abolishes synaptic depression during high-frequency synaptic activation and in the posttetanic period. These changes occur without detectable alteration in motoneuron input resistance, EPSP shape, or the invasion of action potentials into the intraspinal group Ia terminal arborizations. The baclofen-induced effects are qualitatively similar to those observed in more accessible synaptic systems when presynaptic Ca2+ influx and, concomitantly, transmitter release are reduced. Based on these and other recent findings regarding the mechanism of action of baclofen and the distribution of its receptors in the spinal cord, we suggest that L-(-)-baclofen modifies frequency modulation of Ia synaptic transmission by reducing presynaptic Ca2+ influx and the concomitant level of transmitter release from Ia afferent terminals. The drug appears to be a useful tool in studies of the ionic mechanisms that control the release of transmitter and its frequency modulation at inaccessible mammalian synapses.
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PMID:Activation of type B gamma-aminobutyric acid receptors in the intact mammalian spinal cord mimics the effects of reduced presynaptic Ca2+ influx. 283 43

Elevations of brain gamma-aminobutyric acid (GABA) induced by inhibitors of GABA transaminase (GABA-T) are known to induce a number of functional effects including depression of food intake. The aim of the present study was to determine the brain GABA elevation threshold for changes in feeding and several other behaviours, in an effort to clarify whether feeding changes might be secondary to other functional deficits. To this end, various doses of the GABA-T inhibitors ethanolamine-o-sulfate (EOS) and gamma-vinyl GABA (GVG) were injected intracisternally and effects on whole brain GABA, food and water intake, open field activity, catalepsy indices, pain sensitivity, and core temperature were assessed 24 h later. Progressive increases in brain GABA levels were found to differentially affect the responses studied. At the low end of the continuum, significant decreases in feeding behaviour were associated with relatively modest increases in brain GABA (40-60%). At higher levels of GABA elevation (greater than 100%), changes in motoric functions and rectal temperature became apparent. At still higher levels (greater than 200% increases in brain GABA), significant antinociceptive effects were detected. These results support the notion that feeding decreases induced by low doses of GABA-T inhibitors may reflect a fairly specific effect on appetite mechanisms, but also indicate that with increasingly higher doses several other deficits are likely to contribute to the overall decrease in food intake.
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PMID:Graded increases in brain GABA: differential effects on feeding and other behaviours in rats. 284 56

We have investigated the involvement of gamma-aminobutyric acid (GABA) in depression by quantitating benzodiazepine (BZ) binding sites, the ability of GABA to stimulate BZ binding and glutamic acid decarboxylase activity in frontal and temporal cortex obtained at postmortem examination from 21 suicide victims and 21 age- and sex-matched controls. We limited our study to suicide victims with clear evidence of depression, in the absence of symptoms of other psychiatric disorders. Thirteen of the depressed suicide victims had not been prescribed psychoactive drugs recently and none were found in their blood at postmortem; of the remaining 8 suicides, 6 were receiving antidepressant drugs, alone or in combination with other drugs. The number of BZ binding sites was significantly greater (by 18%) in the frontal cortex of the total group of depressed suicides compared to controls, but did not differ in the temporal cortex. The increase in the number of BZ binding sites in the frontal cortex was of similar magnitude when drug-free (16%), drug-treated (21%) and antidepressant-treated suicides (16%) were compared to matched controls, although the increase was only statistically significant for the drug-treated suicides. The Kd of BZ binding and the ability of GABA to stimulate BZ binding did not differ significantly between controls and the total, drug-free, drug-treated or antidepressant-treated suicides in either cortical area. Glutamic acid decarboxylase activity did not differ significantly between control and suicide groups, but was markedly reduced in subjects dying by carbon monoxide poisoning. The present study provides evidence for a greater number of BZ binding sites in the frontal cortex of depressed suicide victims, which could not clearly be attributed to drug treatment.
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PMID:Brain GABAA/benzodiazepine binding sites and glutamic acid decarboxylase activity in depressed suicide victims. 285 68

Binding sites for gamma-aminobutyric acid, type B (GABAB), were measured in post-mortem brain samples (frontal cortex, temporal cortex, and hippocampus) from a group of suicide victims and a group of sex- and age-matched controls. Retrospective psychiatric diagnosis was performed, and only suicide victims with clear evidence of depression in the absence of symptoms of other psychiatric or neurological disorders were studied. There were no significant differences between depressed suicides and controls in the number or affinity of GABAB binding sites in the frontal or temporal cortex and no difference in GABAB binding (measured at two concentrations) in the hippocampus. Thirteen of the depressed suicides had not been prescribed antidepressant drugs recently, and none were found in their blood at postmortem. The number of GABAB binding sites in the frontal and temporal cortex and GABAB binding in the hippocampus did not differ significantly between these drug-free suicides and matched controls. The Kd was higher, however, in the temporal cortex of the drug-free suicides than in the controls. A significant negative correlation was found between age and the number of GABAB binding sites in the temporal cortex (on the basis of pooled data from suicides and controls). These results indicate that GABAB binding sites are unaltered in the brains of depressed suicide victims.
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PMID:Brain GABAB binding sites in depressed suicide victims. 285 98

The laminar distribution of gamma-aminobutyric acid (GABA) in the superior colliculus of the guinea pig was analyzed. The superficial gray layer, especially the upper half, was found to contain the highest amount, 37.4 +/- 1.1 mmol/kg dry. To investigate the role of GABA in the superficial gray layer, the effect of GABA on neurotransmission in the superficial gray layer was studied in superior colliculus slices in a perfusion system. Bath-applied GABA, 100 microM-1 mM, enhanced the amplitude of the postsynaptic field potential (PSP) in the superficial gray layer dose dependently and at concentrations above 1 mM it depressed the PSP dose dependently. A similar response pattern was obtained with muscimol (0.1-10 microM, enhancement; greater than 10 microM, depression). However, (-)-baclofen only inhibited the PSP dose dependently (0.1-1 microM). The excitatory effect of GABA was enhanced at concentrations of nipecotic acid less than 0.5 mM. Bicuculline 1 microM shifted the dose-response curve of GABA to the right and the excitatory effect was also enhanced. These results indicate that GABA has a dual action on neurotransmission in the superficial gray layer: an excitatory effect, possibly mediated by GABAA receptors and an inhibitory effect mediated by both GABAA and GABAB receptors.
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PMID:Excitatory and inhibitory action of GABA on synaptic transmission in slices of guinea pig superior colliculus. 285 12


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