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

Energy deprivation, as a result of aglycemia, leads to depression of the central synaptic transmission. Endogenous adenosine has been implicated in this depressant effect. We have studied the possible involvement of endogenous adenosine in the depression of corticostriatal excitatory transmission induced by glucose deprivation by using intracellular recordings in brain slices. After stimulation of corticostriatal fibers, EPSPs were recorded from striatal spiny neurons. Adenosine (3-300 microM) or brief periods (5-10 min) of aglycemia reduced the EPSP amplitude but did not alter the membrane potential and the resistance of the recorded cells. These inhibitory effects were not associated with an alteration of the postsynaptic sensitivity to exogenous glutamate but were coupled with an increased paired-pulse facilitation, suggesting the involvement of presynaptic mechanisms. A delayed postsynaptic membrane depolarization/inward current was detected after 15-20 min of glucose deprivation. The presynaptic inhibitory effects induced by adenosine and aglycemia were both antagonized either by the nonselective adenosine receptor antagonist caffeine (2.5 mM) or by the A1 receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine (CPT, 1 microM) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300 nM). Conversely, these antagonists affected neither the delayed membrane depolarization/inward current nor the underlying conductance increase produced by glucose deprivation. The ATP-sensitive potassium channel blockers tolbutamide (1 mM) and glipizide (100 nM) had no effect on the aglycemia-induced decrease of EPSP amplitude. Our data demonstrate that endogenous adenosine acting on A1 receptors mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses, whereas ATP-dependent potassium channels do not play a significant role in this presynaptic inhibition.
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PMID:Endogenous adenosine mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses. 916 11

The effects of adenosine (100 nM, icv), dipyridamole (DPM, 5 mg/kg, i.p.), adenosine A1 receptor antagonist 8-cyclopentyl-theophylline (8-CPT, 10 mg/kg, i.p.), and aminophylline (AMP) and caffeine (CAF) (at equivalent doses of 35 mg/kg, i.p.), were examined in rats. Anti-epileptic drugs (AEDs) were also administered i.p., viz, carbamazepine (CBZ, 10 mg/kg); phenobarbitone (PB, 10 mg/kg); phenytoin (PHT, 20 mg/kg); valproic acid (VPA, 300 mg/kg); and diazepam (DZP, 10 mg/kg), to study their effects on EEG after discharge (AD) and postictal depression (PID) induced by cortical stimulation. The AD parameters: (1) duration of EEG-AD (sec) and (2) number of spikes was noted both during pre and post drug treatment sessions. Adenosine and DPM had no special effects on AD parameters but showed significant prolongation of PID. All the adenosine antagonists, 8-CPT, AMP and CAF produced significant prolongation of AD duration, increase in number of spikes and reduced the duration of PID to a significant extent. Interestingly, some of the AEDs, viz. CBZ, VPA and DZP showed abolition of all the EEG-AD parameters whereas PB and PHT failed to show any significant effect. The results confirm previous findings on involvement of adenosine in postictal events.
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PMID:Influence of adenosine, dipyridamole, adenosine antagonists and antiepileptic drugs on EEG after discharge following cortical stimulation. 931 32

Obsessive-compulsive disorder (OCD) sufferers have long been observed to give excessive consideration to normally ignored exogenous and endogenous stimuli. This over-focused attention concerning their symptoms has led researchers to experimentally investigate the attentional mechanisms involved in this disorder and its psychobiological basis. Previous psychometric and neuropsychological research has demonstrated the validity of the sub-clinical analogue in the study of the mechanisms underlying OCD. In this study, 71 introductory university students were recruited from an original pool of 450 people on the basis of their scores on the Spanish version of the Padua Inventory. A high obsessive group (n = 35) was compared with a control group (n = 36) on a standard sustained attention task: the Continuous Performance Test, Identical Pairs version (CPT-IP). The results showed a significant interaction effect between CPT-IP subscales (verbal and spatial) and group membership. This effect was more evident among men. The results were unrelated to general intelligence, depression, anxiety, personality or motivational factors. These findings support the hypothesis that neuropsychological deficits in OCD may be related to a hemispheric functional imbalance rather than to a lateralised dysfunction of a particular hemisphere.
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PMID:Hemispheric functional imbalance in a sub-clinical obsessive-compulsive sample assessed by the Continuous Performance Test, Identical Pairs version. 933 2

We have studied the possible mechanisms underlying the decrease of excitatory transmission induced by glucose deprivation by using electrophysiological recordings in corticostriatal slices. Extracellular field potentials were recorded in the striatum after cortical stimulation; these potentials were progressively reduced by glucose deprivation. The reduction started 5 minutes after the onset of aglycemia. The field potential was fully suppressed after 40 minutes of glucose deprivation. After the washout of the aglycemic solution only a partial recovery was observed. Aglycemia also induced a delayed inward current during single-microelectrode voltage-clamp recordings from spiny neurons. This inward current was coupled with an increased membrane conductance. The A1 adenosine receptor antagonists, 8-cyclopentyl-1,3-dimethylxanthine (CPT, 1 micromol/L) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300 nmol/L), significantly reduced the aglycemia-induced decrease of field potential amplitude. Moreover, in the presence of CPT and CPX, a full recovery of the field potential amplitude after the interruption of the aglycemic solution was observed. Conversely, these antagonists affected neither the inward current nor the underlying conductance increase produced by glucose deprivation. The ATP-sensitive potassium channel blockers glibenclamide (10 micromol/L) and glipizide (100 nmol/L) had no effect on the aglycemia-induced decrease of the field potential amplitude. We suggest that endogenous adenosine, but not ATP-dependent potassium channels, plays a significant role in the aglycemia-induced depression of excitatory transmission at corticostriatal synapses probably through a presynaptic mechanism. Moreover, adenosine is not involved in the postsynaptic changes induced by glucose deprivation in spiny striatal neurons.
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PMID:A possible mechanism for the aglycemia-induced depression of glutamatergic excitation in the striatum. 934 37

Our previous findings indicated that electrical or chemical activation of the thalamic nucleus submedius (Sm) produced significant antinociceptive effects and that these effect were blocked by lesion or depression of the ventrolateral orbital cortex (VLO) or the periaqueductal gray (PAG) suggesting a role of the Sm in modulation of nociception. To further investigate the neurotransmitter mechanism involved in this nociceptive modulatory pathway, we tested the effects of microinjection of 5-hydroxytryptamine (5-HT, 50 mM, 0.5 microl) into Sm on the tail flick (TF) reflex. The results show that a unilateral microinjection of 5-HT into Sm significantly depresses the TF reflex; and that this effect is repeatable and dose-dependent. Furthermore, microinjection of 5-HT2 receptor antagonist cyproheptadine (CPT, 0.3 mM, 0.5 microl) into the same Sm site reverses this 5-HT-evoked inhibition of TF reflex. These results suggest that 5-HT application to the Sm may activate Sm neurons through the 5-HT2 receptors leading to activation of the brainstem descending inhibitory system via the VLO and depression of the nociceptive information at the spinal level.
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PMID:Inhibitory effects of 5-hydroxytryptamine microinjection into thalamic nucleus submedius on rat tail flick reflex are mediated by 5-HT2 receptors. 1002 5

Nitric oxide (NO) donors were recently shown to produce biphasic contractile effects in cardiac tissue, with augmentation at low NO levels and depression at high NO levels. We examined the subcellular mechanisms involved in the opposing effects of NO on cardiac contraction and investigated whether NO modulates contraction exclusively via guanylyl cyclase (GC) activation or whether some contribution occurs via cGMP/PKG-independent mechanisms, in indo 1-loaded adult cardiac myocytes. Whereas a high concentration of the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 100 micromol/L) significantly attenuated contraction amplitude by 24.4+/-4.5% (without changing the Ca2+ transient or total cAMP), a low concentration of SNAP (1 micromol/L) significantly increased contraction amplitude (38+/-10%), Ca2+ transient (26+/-10%), and cAMP levels (from 6.2 to 8.5 pmol/mg of protein). The negative contractile response of 100 micromol/L SNAP was completely abolished in the presence of the specific blocker of PKG KT 5823 (1 micromol/L); the positive contractile response of 1 micromol/L SNAP persisted, despite the presence of the selective inhibitor of GC 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 micromol/L) alone, but was completely abolished in the presence of ODQ plus the specific inhibitory cAMP analog Rp-8-CPT-cAMPS (100 micromol/L), as well as by the NO scavenger oxyhemoglobin. Parallel experiments in cell suspensions showed significant increases in adenylyl cyclase (AC) activity at low concentrations (0.1 to 1 micromol/L) of SNAP (AC, 18% to 20% above basal activity). We conclude that NO can regulate both AC and GC in cardiac myocytes. High levels of NO induce large increases in cGMP and a negative inotropic effect mediated by a PKG-dependent reduction in myofilament responsiveness to Ca2+. Low levels of NO increase cAMP, at least in part, by a novel cGMP-independent activation of AC and induce a positive contractile response.
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PMID:Activation of distinct cAMP-dependent and cGMP-dependent pathways by nitric oxide in cardiac myocytes. 1032 39

1. The effects of adenosine on synaptic transmission in magnocellular neurosecretory cells were investigated using whole-cell patch-clamp recordings in acute rat hypothalamic slices that included the supraoptic nucleus. 2. Adenosine reversibly reduced the amplitude of evoked inhibitory (IPSCs) and excitatory (EPSCs) postsynaptic currents in a dose-dependent manner (IC50 approximately 10 microM for both types of current). 3. Depression of IPSCs and EPSCs by adenosine was reversed by the application of the A1 adenosine receptor antagonist 8-cyclopentyl-1, 3-dimethylxanthine (CPT; 10 microM). 4. When pairs of stimuli were given at short intervals, adenosine inhibitory action was always less effective on the second of the two responses than on the first, resulting in an increased paired-pulse facilitation and suggesting a presynaptic site of action. This observation was confirmed by analysis of spontaneous miniature synaptic currents whose frequency, but not amplitude or kinetics, was reversibly reduced by 100 microM adenosine. 5. CPT had no effect on synaptic responses evoked at a low frequency of stimulation (0.05-0.5 Hz), indicating the absence of tonic activation of A1 receptors under these recording conditions. However, CPT inhibited a time-dependent depression of both IPSCs and EPSCs induced during a 1 Hz train of stimuli. 6. Taken together, these results suggest that adenosine can be released within the supraoptic nucleus at a concentration sufficient to inhibit the release of GABA and glutamate via the activation of presynaptic A1 receptors. By its inhibitory feedback action on the major afferent inputs to oxytocin and vasopressin neurones, adenosine could optimally adjust electrical and secretory activities of hypothalamic magnocellular neurones.
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PMID:Adenosine-induced presynaptic inhibition of IPSCs and EPSCs in rat hypothalamic supraoptic nucleus neurones. 1054 29

Several reports have shown that energy deprivation, as a result of hypoxia, hypoglycaemia or ischaemia, depresses excitatory synaptic transmission in virtually all brain areas. How this pathological condition affects inhibitory synaptic transmission is still unclear. In the present in vitro study, we coupled whole-cell patch clamp recordings from striatal neurones with focal stimulation of GABAergic nerve terminals in order to characterize the electrophysiological effects of combined oxygen and glucose deprivation (in vitro ischaemia) on inhibitory postsynaptic currents (IPSCs) in this brain area. We found that brief periods (2-5 min) of in vitro ischaemia invariably caused a marked depression of IPSC amplitude. This inhibitory effect was fully reversible on removal of the ischaemic challenge. It was coupled with an increased paired-pulse facilitation, suggesting the involvement of presynaptic mechanisms. Accordingly, the ischaemic inhibition of striatal GABAergic IPSCs was not caused by a shift in the reversal potential of GABA(A)-receptor mediated synaptic currents, and was independ- ent of postsynaptic ATP concentrations. Endogenous adenosine, acting on A1 receptors, appeared responsible for this presynaptic action as the ischaemic depression of IPSCs was prevented by CPT [8-(4-chlorophenylthio) adenosine] and DPCPX, two adenosine A1 receptor antagonists, and mimicked by the application of adenosine in the bathing solution. Conversely, ATP-sensitive potassium channels were not involved in the inhibition of IPSCs by ischaemia, as demonstrated by the fact that tolbutamide and glipizide, two blockers of these channels, were ineffective in preventing this electrophysiological effect. The early depression of GABA-mediated synaptic transmission might play a role in the development of irreversible neuronal injury in the course of brain ischaemia.
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PMID:Adenosine-mediated inhibition of striatal GABAergic synaptic transmission during in vitro ischaemia. 1152 87

Recent evidence points to a potential role of cyclic GMP (cGMP) in the control of cardiac glucose utilization. The present work examines whether the glucose transport system of cardiac myocyte is a site of this cGMP-dependent regulation. Treatment of isolated rat cardiomyocytes (for 10 min) with the membrane-permeant cGMP analogue 8-(4-chlorophenylthio)-cGMP (8-p-CPT-cGMP, 200 microM) caused a decrease in glucose transport in non-stimulated (basal) myocytes, as well as in cells stimulated with insulin or with the mitochondrial inhibitor oligomycin B by up to 40%. An inhibitory effect was also observed with another cGMP analogue (8-bromo-cGMP), and in cells stimulated by hydrogen peroxide or anoxia. In contrast, 8-p-CPT-cAMP (200 microM), or the beta-adrenergic agonist isoprenaline (which increases cAMP levels) did not depress glucose transport, and even potentiated the effect of insulin. Blockade of endogenous cGMP formation with the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) significantly increased basal and insulin-dependent glucose transport (by 25%), whereas addition of the guanylate cyclase activator 3-(5'-hydroxymethyl-2'furyl)-1-benzylindazol (YC-1, 30 microM) produced a depression of glucose transport (by 20%). Confocal laser scanning microscopic studies revealed that cGMP partially prevents the insulin-induced redistribution of the glucose transporter GLUT4 from intracellular stores to the cell surface. These observations suggest that the glucose transport system of cardiomyocytes represents a metabolic target of inhibition by cGMP, and that this regulation occurs at the level of the trafficking of glucose transporters.
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PMID:Inhibition of glucose transport by cyclic GMP in cardiomyocytes. 1153 Nov 63

The mechanisms underlying the depression of evoked fast excitatory postsynaptic currents (EPSCs) following superfusion with medium deprived of oxygen and glucose (in vitro ischemia) for a 4-min period in hippocampal CA1 neurons were investigated in rat brain slices. The amplitude of evoked fast EPSCs decreased by 85 +/- 7% of the control 4 min after the onset of in vitro ischemia. In contrast, the exogenous glutamate-induced inward currents were augmented, while the spontaneous miniature EPSCs obtained in the presence of tetrodotoxin (TTX, 1 microM) did not change in amplitude during in vitro ischemia. In a normoxic medium, a pair of fast EPSCs was elicited by paired-pulse stimulation (40-ms interval), and the amplitude of the second fast EPSC increased to 156 +/- 24% of the first EPSC amplitude. The ratio of paired-pulse facilitation (PPF ratio) increased during in vitro ischemia. Pretreatment of the slices with adenosine 1 (A1) receptor antagonist, 8-cyclopenthyltheophiline (8-CPT) antagonized the depression of the fast EPSCs, in a concentration-dependent manner: in the presence of 8-CPT (1-10 microM), the amplitude of the fast EPSCs decreased by only 20% of the control during in vitro ischemia. In addition, 8-CPT antagonized the enhancement of the PPF ratio during in vitro ischemia. A pair of presynaptic volleys and excitatory postsynaptic field potentials (fEPSPs) were extracellularly recorded in a proximal part of the stratum radiatum in the CA1 region. The PPF ratio for the fEPSPs also increased during in vitro ischemia. On the other hand, the amplitudes of the first and second presynaptic volley, which were abolished by TTX (0.5 microM), did not change during in vitro ischemia. The maximal slope of the Ca(2+)-dependent action potential of the CA3 neurons, which were evoked in the presence of 8-CPT (1 microM), nifedipine (20 microM), TTX (0.5 microM), and tetraethyl ammonium chloride (20 mM), decreased by 12 +/- 6% of the control 4 min after the onset of in vitro ischemia. These results suggest that in vitro ischemia depresses the evoked fast EPSCs mainly via the presynaptic A1 receptors, and the remaining 8-CPT-resistant depression of the fast EPSCs is probably due to a direct inhibition of the Ca(2+) influx to the axon terminals.
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PMID:Mechanisms underlying the depression of evoked fast EPSCs following in vitro ischemia in rat hippocampal CA1 neurons. 1153 60


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