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

Spinal cords were maintained in vitro and suction electrodes used to record activity in lumbar 4 or 5 ventral roots. Stimulation of the latero-ventral aspect of the thoracic cord elicited fast and slow responses on the same and on the opposite side of the cord. There were 5 distinct responses: ipsilaterally a short latency (d ISL), a polysynaptic and a slow response, and contralaterally a fast (d CON FAST) and a slow response. The largest amplitude component, d ISL, may arise from stimulation of propriospinal neurones; the other responses may arise from stimulation of descending pathways. The slow responses had half decay times of 13-15 s and required a high intensity stimulus to elicit a maximal response. All 5 responses were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione suggesting that kainate/AMPA receptors were involved in their generation. In addition, NMDA receptors were involved in generation of the slow responses. Potentiation of certain responses by the 5-HT2 antagonists, ketanserin, ritanserin and Lilly 53837, indicated that endogenous 5-HT was exerting a modulatory depression of these responses. In addition to eliciting the 5 responses, thoracic cord stimulation caused an inhibition of segmental reflexes evoked from the lumbar dorsal root. Exogenous 5-HT, 8-hydroxy-2-(di-n-propylamino) tetralin, 5-carboxamidotryptamine, dipropyl-5-carboxamido-tryptamine and methysergide depressed all or some of the descending responses. Blockade of adrenoceptors using yohimbine, idazoxan, prazosin or propranolol had no unequivocal effect suggesting that the release of endogenous catecholamines was minimal. Clonidine was a potent depressant of the slow responses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pharmacology of descending responses evoked by thoracic stimulation in the neonatal rat spinal cord in vitro. 810 94

Relationships between caffeine dose, methylxanthine tissue concentrations, adenosine receptor binding and locomotor activity were examined in CD-1 mice. A method of caffeine infusion via s.c. pumps provided constant steady-state methylxanthine concentrations. Mice receiving caffeine doses of 97 mg/kg/day (with mean plasma concentration of 2.7 micrograms/ml) demonstrated motor activity depression for 6 days after pump implantation (vs. vehicle-treated controls). Mice receiving caffeine doses of 194 mg/kg/day (mean plasma concentration of 7.1 micrograms/ml) demonstrated motor stimulation 4 and 24 hr after implantation. Mice receiving this dose for 6 days developed motor depression. A reduction in the stimulant effects of acute caffeine (20 mg/kg i.p.) was found in mice receiving caffeine infusions (194 mg/kg/day for 6 days) as compared to those receiving vehicle infusions, suggestive of drug tolerance. These dose- and time-dependent behavioral effects during caffeine-infusion were associated with decreases between 20 and 69% in specific binding of A1 adenosine radioligand 1,3-[3H]dipropyl-8-cyclopentylxanthine in vivo. Behavioral alterations during caffeine infusion appear to be mediated by A1 adenosine receptor occupancy. Increasing motor depression developed on days 1 and 2 after pump removal with values returning to control levels by days 4 and 6. Behavioral alterations were associated with in vivo binding increases of 98 and 324%, respectively, and a return to control values on days 4 and 6. In vivo binding alterations were not associated with ex vivo A1 receptor binding changes. Caffeine tolerance and withdrawal effects in this animal model appear to be mediated by chronic occupancy of A1 adenosine receptors. The behavioral and in vivo receptor binding alterations observed after caffeine discontinuation follow a time course similar to caffeine withdrawal in humans.
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PMID:Caffeine treatment and withdrawal in mice: relationships between dosage, concentrations, locomotor activity and A1 adenosine receptor binding. 837 Nov 58

Endogenous interstitial adenosine may protect the hypoxic heart by attenuating beta-adrenergic-induced contractile and metabolic responses, thereby reducing energy utilization. Constant-flow perfused rat hearts were used to study: 1) the effect of hypoxia on isoproterenol (ISO)-induced increase in interstitial adenosine, as estimated with epicardial surface transudates, and 2) the role of endogenous adenosine in hypoxic depression of ISO-induced contractile responses. ISO (1 nM for 10 minutes) in the normoxic heart increased transudate adenosine 114% from a pre-ISO normoxic value of 343 pmol/ml. ISO administered to the hypoxic heart increased transudate adenosine 357% from a pre-ISO hypoxic value of 797 pmol/ml. The absolute magnitude of the ISO-induced increase in transudate adenosine was 625% greater during hypoxia than during normoxia. This was associated with a reduction in the ISO-induced contractile response during hypoxia. In other experiments, with normoxia ISO (10 nM for 10 seconds) increased developed left ventricular pressure by 140 mm Hg, and the maximum rates of left ventricular pressure development and relaxation by 5,860 and 2,771 mm Hg/sec, respectively, above control values of 90 mm Hg, 2,250 mm Hg/sec, and 1,875 mm Hg/sec. Hypoxia reduced the three ISO-induced contractile responses by 50%, 56%, and 36%. However, 1,3-dipropyl-8-cyclopentylxanthine (5 x 10(-7) M), an adenosine A1-receptor antagonist, added to the hypoxic hearts resulted in only a 31%, 39%, and 9% reduction in the ISO-induced responses in developed left ventricular pressure and the maximum rates of left ventricular pressure development and relaxation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypoxia enhances isoproterenol-induced increase in heart interstitial adenosine, depressing beta-adrenergic contractile responses. 838 22

High-frequency stimulation (HFS) of afferent fibers produced short-term depression (STD) and long-term depression (LTD) of corticostriatal synaptic transmission. Application of the non-selective adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) or the selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked the induction of STD but not LTD. Application of adenosine or the selective A1 receptor agonist R(-)N6-(2-phenylisopropyl)adenosine (R-PIA) induced synaptic depression, while the A2a receptor agonist CGS 21680 did not consistently alter synaptic transmission. Depression induced by adenosine or R-PIA was not accompanied by changes in postsynaptic input resistance and appeared to involve a presynaptic depressant effect previously characterized at this synapse. These observations indicate that HFS leads to the production of endogenous adenosine that acts on presynaptic A1 receptors to initiate STD at corticostriatal synapses. Initiation and maintenance of LTD appear to be independent of A1 receptor activation.
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PMID:Activation of adenosine A1 receptors initiates short-term synaptic depression in rat striatum. 858 33

Diallyl disulfide (DADS), an oil-soluble organosulfur compound in processed garlic, was more effective in inhibiting the in vitro growth of human tumor cell lines: HCT-15 (colon), A549 (lung), and SK MEL-2 (skin) than isomolar quantities of the water-soluble compound S-allyl cysteine (SAC). Addition of DADS (100 microM) was cytostatic to all three cell lines. The importance of the allyl and the disulfide groups were revealed by the lack of a comparable depression in the growth of HCT-15 cells exposed to its saturated analogue, dipropyl disulfide (DPDS). Treatment with DADS also resulted in a dose-dependent increase in intracellular free calcium in cells. A dose-dependent decrease in the activity of calcium-dependent ATPase enzyme occurred in HCT-15 cells exposed to increasing quantities of DADS. A correlation (r = -0.975) was found between the intracellular free calcium levels and the Ca-ATPase activity in DADS-treated cells. These studies document that DADS, a constituent of garlic oil, is an effective inhibitor of the growth of human neoplastic cells. Alterations in calcium hemostasis are likely involved in the growth inhibition/cytotoxicity caused by DADS.
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PMID:Diallyl disulfide inhibits the proliferation of human tumor cells in culture. 861 41

1. We have studied three hypoxia-induced phenomena in the CA1 stratum pyramidale of the rat hippocampal slice: (a) the increase in extracellular potassium ion concentration ([K+]e) measured with ion-sensitive microelectrodes, (b) the intracellularly-recorded pyramidal cell hyperpolarization and (c) the extracellularly-recorded depression of the synaptically-evoked field potential recorded in stratum pyramidale. 2. The extracellular potassium ion concentration ([K+]e) rose from 3 mM to 4.1-4.4 mM at a time when the pyramidal cells hyperpolarized by about 6 mV and neurotransmission was virtually abolished. 3. Presumed glial cells depolarized in response to hypoxia. The shape and time course of this response was remarkably similar to the rise in [K+]e so induced. This is consistent with findings that glial cell membrane potential is dependent on transmembrane K+ gradient. 4. We investigated the effects of theophylline (100 microM) and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 microM) on these effects. We have found that these compounds attenuated by about half the hypoxia-induced increase in [K+]e; however, they did not reduce the hypoxia-induced hyperpolarization. We have confirmed that they dramatically reduced the suppression of excitatory transmission caused by the hypoxia. We conclude that adenosine A1 receptors may be involved in the alteration of K+ homeostasis in the hippocampal slice during hypoxia.
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PMID:Action of adenosine receptor antagonists on hypoxia-induced effects in the rat hippocampus in vitro. 864 Mar 53

1. Purine analogues have been examined for anxiolytic- and anxiogenic-like activity in mice, by use of the elevated plus-maze. 2. The selective A1 receptor agonist, N6-cyclopentyladenosine (CPA) had marked anxiolytic-like activity at 10 and 50 microg kg(-1), with no effect on locomotor performance at these doses. 3. The A1 selective adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (CPX) had no significant effect on anxiety-related measures or locomotor behaviour, but blocked the anxiolytic-like activity of CPA. The hydrophilic xanthine, 8-(p-sulphophenyl) theophylline did not prevent anxiolysis by CPA. 4. Caffeine had anxiogenic-like activity at 30 mg kg(-1) which was prevented by CPA at 50 micro kg(-1). 5. The A2 receptor agonist, N6-[2-(3,5-dimethoxyphenyl)-2(2-methylphenyl)-ethyl]adenosine (DPMA) had no effect on anxiety behaviour but depressed locomotor activity at the highest dose tested of 1 mg kg(-1). The A2 receptor antagonist, 1,3-dimethyl-l-propargylxanthine (DMPX) had no effect on anxiety-related measures or locomotion and did not modify the anxiolytic-like activity of CPA. 6. Administration of DPMA in combination with anxiolytic doses of CPA prevented the anxiolytic-like activity of the latter. 7. The results suggest that the selective activation of central A1 adenosine receptors induces anxiolytic-like behaviour, while the activation of A2 sites causes locomotor depression and reduces the effects of A1 receptor activation. The absence of any effect of CPX alone suggests that the receptors involved in modulating behaviour in the elevated plus-maze in mice are not activated tonically by endogenous adenosine.
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PMID:Anxiolytic activity of adenosine receptor activation in mice. 864 Mar 55

This study tested the hypothesis that endogenous adenosine, a neuromodulator which is known to modify long-term potentiation (LTP), might also affect other forms of long-lasting synaptic plasticity, namely long-term depression (LTD) and depotentiation, in the hippocampus. Long-term depression was induced by applying low-frequency stimulation (LFS; 1 Hz, 900 stimuli, test intensity) to the Schaffer collateral-commissural fibres in hippocampal slices taken from young (12-14-day old) animals. Depotentiation was induced by delivering LFS to a pathway in which LTP had previously been saturated. Under control conditions, LTD induced in two distinct pathways was similar. However, low-frequency stimulation, applied in either pathway in the presence of the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 nM), resulted in LTD which was larger than in control conditions. In a similar way, while under control conditions depotentiation induced in two distinct pathways was similar, when LFS was applied in the presence of DPCPX (10 nM) facilitation of depotentiation was observed. These results suggest that endogenous adenosine, acting through adenosine A1 receptors, is able to attenuate long-term depression and depotentiation in the hippocampus.
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PMID:Endogenous adenosine attenuates long-term depression and depotentiation in the CA1 region of the rat hippocampus. 914 53

We describe how endogenous adenosine can prevent the induction of homosynaptic long-term depression (LTD) in the CA1 region of slices of adult rat hippocampus. Neither of two consecutive periods of prolonged low frequency stimulation (LFS; 1 Hz, 900 stimuli) of the Schaffer collateral-commissural fibres resulted in the induction of LTD in the CA1 region of hippocampal slices from adult (8-30 week) animals. However, in the presence of adenosine deaminase or the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentyl-xanthine (DPCPX), LTD was induced by each of the first and second of two periods of LFS. The first period of LFS did not, but the second period of LFS did, induce LTD in the presence of DPCPX and the NMDA receptor antagonist, D-2-amino-5-phosphonopentanoate (AP5). The present results show that A1 receptor activation by endogenous adenosine can prevent the induction of LTD in the adult hippocampus.
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PMID:A role for adenosine in the regulation of long-term depression in the adult rat hippocampus in vitro. 914 2

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


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