dizocilpine-maleate and 1-3-dipropyl-8-cyclopentylxanthine

Neuropathic pain is relatively common and occurs in approximately 6-8% of the population. It is associated with allodynia and hyperalgesia. Thus, non-pharmacological treatments, such as transcranial direct current stimulation (tDCS) may be useful for relieving pain.. This study aimed to investigate the antiallodynic effect of tDCS in a mice model of neuropathic pain, and the underlying neurotransmission systems that could drive these effects.. Male, Swiss mice, weighing 25-35 g, were subjected to partial sciatic nerve ligation (PSNL). Allodynia was assessed using a Von Frey filament (0.6 g). First, the behavioral time-course of these mice was assessed after 5, 10, 15 and 20 min of tDCS (0.5 mA). Second, the mice that underwent PSNL were assigned to either the tDCS (0.5 mA, 15 min) or tDCS sham group, and further assigned to receive either saline or a drug (i.e., naloxone, yohimbine, a-methyl-p-tyrosine, q-chlorophenylalanine methyl ester, caffeine, 1,3-dipropyl-8-cyclopentylxanthine, AM281, AM630, flumazenil, MK-801, or lidocaine).. The antiallodynic effect of tDCS lasted 2 h and 4 h, after 10 min and 15 or 20 min of treatment, respectively (P < .001, P < .01, and P < .05, respectively). The antiallodynic effect of tDCS was associated with all the systems that were analyzed, i.e., the opioidergic (P < .01), adenosinergic (P < .001), serotonergic (P < .01), noradrenergic (P < .001), cannabinoid (P < .001), GABAergic, and glutamatergic (P < .001) systems. Lidocaine did not reverse the antiallodynic effect of tDCS (P > .05).. The antiallodynic effect of tDCS was associated with different neurotransmitters systems; the duration of these after-effects depended on the time exposure to tDCS.

Topics: Adenosine A1 Receptor Antagonists; Animals; Caffeine; Central Nervous System Stimulants; Disease Models, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Flumazenil; GABA Modulators; Hyperalgesia; Male; Mice; Morpholines; Naloxone; Narcotic Antagonists; Neuralgia; Pain Threshold; Physical Stimulation; Pyrazoles; Transcranial Direct Current Stimulation; Xanthines

Evidence suggests that pre-ischeamic conditioning (PIC) offers protection against a subsequent ischeamic event. Although some brain areas such as the hippocampus have received much attention, the receptor mechanisms of PIC in other brain regions are unknown. We have previously shown that 10 min oxygen and glucose deprivation (OGD) evokes tolerance to a second OGD event in the caudate. Here we further examine the effect of length of conditioning event on the second OGD event. Caudate mouse brain slices were superfused with artificial cerebro-spinal fluid (aCSF) bubbled with 95%O(2)/5%CO(2). OGD was achieved by reducing the aCSF glucose concentration and by bubbling with 95%N(2)/5%CO(2). After approximately 5 min OGD a large dopamine efflux was observed, presumably caused by anoxic depolarisation. On applying a second OGD event, 60 min later, dopamine efflux was delayed and reduced. We first examined the effect of varying the length of the conditioning event from 5 to 40 min and found tolerance to PIC increased with increasing duration of conditioning. We then examined the receptor mechanism(s) underlying PIC. We found that pre-incubation with either MK-801 or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) reduced tolerance to the second OGD event. These data suggest that either N-methyl-D-aspartate (NMDA) or adenosine A(1) receptor activation evokes PIC in the mouse caudate.

Topics: Adenosine A1 Receptor Antagonists; Animals; Brain Ischemia; Caudate Nucleus; Dizocilpine Maleate; Dopamine; Glucose; Heart Arrest; Ischemic Preconditioning; Male; Mice; Mice, Inbred C57BL; Oxygen; Receptor, Adenosine A1; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Tetrazolium Salts; Xanthines

The aim of this study was to characterize the interaction of adenosine A1-receptor and cannabinoid CB1-receptor antagonists in the water maze and object-location tasks, and to evaluate the participation of glutamatergic neurotransmission in the hippocampus in the learning enhancement induced by the coadministration of both antagonists. Our results show that coadministration of ineffective doses of DPCPX (8-cyclopentyl-1,3-dipropylxanthine) (an A1-receptor antagonist) and AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) (a CB1-receptor antagonist) in different proportions enhanced the acquisition of spatial learning. N-methyl-D-aspartate receptor blockade disrupted the effects of the selected drug combination [AM251 0.25 mg/kg intraperitoneally (i.p.)+DPCPX 0.30 mg/kg i.p.] either in the water maze or in the object-location task. Moreover, this drug combination induced a significant ex-vivo enhancement in glutamate release into hippocampal slices. In addition, the blockade of N-methyl-D-aspartate receptors with MK-801 (0.25 µg/site) infused into the hippocampal CA1 area reversed the effects of coadministration, as evaluated in the object-location task. In conclusion, this is the first study to show that A1-receptor and CB1-receptor antagonists might interact on hippocampal neurons to enhance spatial memory in mice.

Topics: Adenosine A1 Receptor Antagonists; Animals; Dizocilpine Maleate; Glutamic Acid; Hippocampus; Male; Mice; Piperidines; Pyrazoles; Receptor, Cannabinoid, CB1; Spatial Behavior; Synaptic Transmission; Xanthines

The rodent hippocampus exhibits population activities called sharp waves (SPWs) during slow wave sleep and wake immobility. SPWs are important for hippocampal-cortical communication and memory consolidation, and abnormal sharp wave-ripple complexes are closely related to epileptic seizures. Although the SPWs are known to arise from the CA3 circuit, the local mechanisms underlying their generation are not fully understood. We hypothesize that endogenous adenosine is a local regulator of hippocampal SPWs. We tested this hypothesis in thick mouse hippocampal slices that encompass a relatively large hippocampal circuit and have a high propensity of generating spontaneous in vitro SPWs. We found that application of adenosine A1 receptor antagonists induced in vitro SPWs and that such induction was sensitive to blockade by NMDA receptor antagonists. By contrast, an increase in endogenous adenosine via pharmacological inhibition of adenosine transporters or adenosine degrading enzymes suppressed spontaneous in vitro SPWs. We thus suggest that the initiation and incidence of sharp wave-like population events are under tight control by the activity of endogenously stimulated A1 receptors.

Topics: Adenine; Adenosine; Adenosine A1 Receptor Antagonists; Animals; Dizocilpine Maleate; Electric Stimulation; Excitatory Postsynaptic Potentials; Hippocampus; In Vitro Techniques; Inhibitory Postsynaptic Potentials; Membrane Potentials; Mice; Mice, Inbred C57BL; Microelectrodes; Nucleoside Transport Proteins; Patch-Clamp Techniques; Pyramidal Cells; Quinoxalines; Receptor, Adenosine A1; Receptors, N-Methyl-D-Aspartate; Theophylline; Xanthines

Interactions between adenosine receptor ligands and dizocilpine (uncompetitive NMDA receptor antagonist) was studied in antinociceptive, writhing test in mice. Minimal effective, antinociceptive doses of adenosine receptor agonists were: 0.1 mg/kg (NECA--A1/A2 agonist). Generally, these agonists did not potentiate the subthreshold dose of dizocilpine (0.05 mg/kg). Of all adenosine receptor antagonists used, only caffeine (A2 and A2 antagonists) reversed dizocilpine-induced (0.1 mg/kg) antinociception dose-dependently. These findings indicate that dizocilpin-induced antinociception in the writhing test is only partly influenced by adenosine receptor ligands.

Topics: Acetic Acid; Animals; Behavior, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Male; Mice; Nociceptors; Pain; Purinergic P1 Receptor Agonists; Receptors, Purinergic P1; Theobromine; Xanthines

Adenosine receptor antagonists initiate repetitive bursting activity in the CA3 region of hippocampal slices. Although some studies have suggested that this effect is irreversible, this has been difficult to establish because many adenosine antagonists wash out of brain slices extremely slowly. Furthermore the cellular mechanism that underlies persistent bursting is unknown. To resolve these issues, we studied the effects of nonselective (8-p-sulfophenyltheophylline, 8SPT, 50-100 microM), A(l)-selective (8-cyclopentyl-1, 3-dipropylxanthine, 100 nM; xanthine carboxylic acid congener, 200 nM), and A(2A)-selective (chlorostyryl-caffeine; 200 nM) adenosine antagonists in the CA3 region of rat hippocampal slices using extracellular recording. Superfusion with all of the adenosine antagonists except chlorostyryl-caffeine induced bursting, and the burst frequency after 30 min drug superfusion did not differ for the different antagonists. Most slices showed a period of rapid initial bursting, followed either by stable bursting at a lower frequency or a pattern of oscillating burst frequency. In either case, the bursting continued after drug washout. Virtually identical patterns of long-term bursting activity were observed when 8SPT was washed out or applied continuously. Control experiments using exogenous adenosine to characterize the persistence of 8SPT in tissue demonstrated >95% washout at 60 min, a time when nearly all slices still showed regular bursting activity. When the N-methyl-D-aspartate (NMDA) antagonists DL-2-amino-5-phosphonovaleric acid (AP5; 50 microM) or dizocilpine (10 microM) were applied before and during 8SPT superfusion, bursting occurred in the presence of the NMDA antagonists but did not persist once the 8SPT was washed out. AP5 had no effect on persistent bursting when applied after the initiation of spiking. The selective calcium/calmodulin-dependent protein kinase inhibitor 1-[N, O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62; 3 microM), which has been shown to block NMDA receptor-dependent synaptic plasticity in the CA1 region, also significantly decreased the long-term effect of 8SPT. Thus adenosine antagonists initiate persistent spiking in the CA3 region; this activity does not depend on continued occupation of adenosine receptors by antagonists, and can be blocked by treatments that prevent NMDA receptor-dependent plasticity.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; 2-Amino-5-phosphonovalerate; Adrenergic Antagonists; Animals; Caffeine; Dizocilpine Maleate; Enzyme Inhibitors; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Hippocampus; Male; N-Methylaspartate; Neuronal Plasticity; Neurons; Periodicity; Purinergic P1 Receptor Antagonists; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Second Messenger Systems; Theophylline; Xanthines

The transient property of the dipyridamole-induced depression of excitatory synaptic transmission was analyzed using field EPSPs (fEPSPs) recorded from the CA1 region in rat hippocampal slices. The fEPSPs were depressed by 1 microM dipyridamole and then gradually recovered to the control level. The depression was antagonized by aminophylline or DPCPX, although it was not significantly affected by DMPX. The results suggest that the fEPSP depression is induced by a mechanism through the A(1) receptor.

Topics: Adenosine; Aminophylline; Analgesics; Animals; Bicuculline; Dipyridamole; Dizocilpine Maleate; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Feedback; GABA Antagonists; Glyburide; Hippocampus; Hypoglycemic Agents; Male; Naphthalenes; Neomycin; Neurons; Neurotransmitter Agents; Phosphodiesterase Inhibitors; Protein Kinase C; Protein Synthesis Inhibitors; Rats; Rats, Wistar; Receptors, Purinergic P1; Synaptic Transmission; Xanthines

The Y-maze was used to assess spontaneous alternation behaviour in mice to examine possible interactions between the N-methyl-D-aspartate receptor channel blocker dizocilpine and purine receptor agonists and antagonists. Scopolamine reduced spontaneous alternation. Dizocilpine also produced a dose-dependent reduction in alternation scores, which was accompanied by an increase in locomotion. The selective A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) had no effect when administered alone, or in combination with scopolamine. However, when co-administered with dizocilpine, CPX reversed both the deficit in alternation behaviour and also the increase in locomotion induced by dizocilpine. The A1 selective agonist N6-cyclopentyladenosine (CPA) had no effect on either locomotion or alternation scores when administered alone, but in combination with scopolamine, CPA attenuated the scopolamine-induced deficit. CPA had no significant effect on the dizocilpine-induced deficit. The A2 selective agonist N6-[2-(3, 5-dimethoxyphenyl)-2(2-methylphenyl)-ethyl]adenosine (DPMA), had no effect on spontaneous alternation when administered alone, but did cause a depression of locomotion. DPMA had no significant effect when co-administered with scopolamine, but reversed the deficit in spontaneous alternation, and the increase in locomotion induced by dizocilpine. The A2 selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) had no effect when given alone or in combination with scopolamine, but when co-administered with dizocilpine, DMPX reversed the reduction in spontaneous alternation caused by dizocilpine. It is concluded that dizocilpine has a detrimental effect on spontaneous alternation which is mediated partly by A1 and A2 adenosine receptors.

Topics: Adenosine; Animals; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Male; Maze Learning; Memory; Mice; Muscarinic Antagonists; Receptors, Purinergic P1; Scopolamine; Xanthines

Systemically administered kainate (10 mg.kg-1) caused neuronal loss in both the hippocampus and the entorhinal regions of the rat brain. This resulted in a loss of 68.3 +/- 13.8 and 53.3 +/- 12.8% of pyramidal neurones in the hippocampal CA1 and CA3a regions, respectively. Chlormethiazole attenuated the loss of neurones in the hippocampal cell layers CA1 (cell loss 10 +/- 3.2%) and CA3a (cell loss 10 +/- 7.7%). The neuroprotective activity of chlormethiazole was apparent in the presence or absence of a low dose of clonazepam (200 micrograms.kg-1 i.p.). The kainate-induced damage could also be measured by the increase in binding of the peripheral benzodiazepine ligand ([3H]PK11195) in the hippocampus. In kainate-treated rats there was a 350-500% increase in binding indicative of reactive gliosis. Chlormethiazole prevented this elevation in a dose- and time-dependent manner, with an ED50 of 10.64 mg.kg-1 and an effective therapeutic window from 1 to 4 h posttreatment. Dizocilpine also attenuated damage significantly. The GABAA agonist muscimol was also able to attenuate the increase in [3H]PK11195 binding in a dose-dependent manner, with an ED50 of approximately 0.1 mg.kg-1. If muscimol, dizocilpine, or the adenosine A1 receptor agonist R-N6-phenylisopropyl-adenosine were administered together with chlormethiazole at their respective ED25 doses, a potentiation was apparent in the degree of neuroprotection. It is concluded that the combination of neuroprotective agents with different mechanisms of action can lead to a synergistic protection against excitotoxicity.

Topics: Adenosine; Animals; Body Temperature; Chlormethiazole; Dizocilpine Maleate; Drug Synergism; Drug Therapy, Combination; Entorhinal Cortex; Epilepsy, Tonic-Clonic; Excitatory Amino Acid Antagonists; GABA Agonists; gamma-Aminobutyric Acid; Gliosis; Hippocampus; Isoquinolines; Kainic Acid; Male; Muscimol; Neurons; Neuroprotective Agents; Neurotoxins; Purinergic P1 Receptor Antagonists; Rats; Rats, Wistar; Xanthines

It has been claimed that blockade of receptors for N-methyl-D-aspartate (NMDA) can enhance adenosine receptor function on single neurones. Previous work has also indicated that the NMDA channel blocker dizocilpine, and the A1 selective agonist N6-cyclopentyladenosine (CPA) both had anxiolytic profiles in the elevated plus-maze. The anxiolytic effect of dizocilpine was accompanied by an increase in locomotor activity. In the present study, the elevated plus-maze has been used to determine whether dizocilpine's effects on behaviour are mediated through activation of adenosine receptors. When co-administered with dizocilpine (0.05 mg/kg), CPA (0.05 mg/kg) reduced the anxiolytic and locomotor effects of dizocilpine. The A1 selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (CPX, 0.05 mg/kg) had no effect when administered alone. When co-administered with dizocilpine, CPX reversed the anxiolytic and increased locomotor effects induced by dizocilpine. The A2 receptor selective agonist N6-[2-(3,5-dimethoxyphenyl)-2(2-methylphenyl)ethyladenosine (DPMA) (1 mg/kg) reversed both the anxiolytic effect and the increased locomotion induced by dizocilpine, while the A2 selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) (1 mg/kg) did not. It is concluded that at least part of the anxiolytic and locomotor stimulant properties of dizocilpine may be explained by the release of endogenous adenosine acting at A1, but not A2 receptors.

Topics: Adenosine; Animals; Dizocilpine Maleate; Drug Interactions; Excitatory Amino Acid Antagonists; Male; Mice; Motor Activity; Receptors, N-Methyl-D-Aspartate; Receptors, Purinergic P1; Xanthines

We have investigated how glucose deprivation in vitro influences the basal and electrically evoked release of dopamine and acetylcholine from rat striatal slices and the role of endogenous activation of NMDA receptors and adenosine A1 receptors in determining the magnitude of this response. Rat striatal slices, preincubated with [3H]dopamine and [14C]choline, were superfused continuously and stimulated electrically. Before and during the second stimulation, some slices were superfused with glucose-free Krebs' solution. Such glucose deprivation caused a 2 to 3-fold increase of the electrically evoked, calcium-dependent release of endogenous adenosine (but not hypoxanthine and inosine) and [3H]dopamine and a 30% increase in release of [14C]acetylcholine. Glucose deprivation also caused a delayed increase in the release of [3H]dopamine, but not of [14C]acetylcholine. The dopamine release was not calcium dependent. The addition of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM), a selective adenosine A1 receptor antagonist, slightly enhanced the glucose deprivation-induced stimulatory effect on the evoked release of these two transmitters, whereas the NMDA receptor antagonist dizocilpine((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine; 3 microM) markedly attenuated the stimulatory effect of glucose deprivation. The change in basal dopamine release was not influenced by DPCPX, but was slightly attenuated by dizocilpine. In summary, the results suggest that lack of substrate induces release of both glutamate, which by actions on presynaptic NMDA receptors causes the release of dopamine, and of adenosine, which via adenosine A1 receptors reduces the electrically evoked release of both dopamine and acetylcholine.

Topics: Acetylcholine; Animals; Calcium; Dizocilpine Maleate; Dopamine; Electric Stimulation; Excitatory Amino Acid Antagonists; Glucose; In Vitro Techniques; Male; Neostriatum; Neurotransmitter Agents; Purinergic P1 Receptor Antagonists; Purines; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Receptors, Purinergic P1; Xanthines

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.

Topics: Adenosine; Animals; Corpus Striatum; Dizocilpine Maleate; Hypoxia; Male; Membrane Potentials; Microelectrodes; Neuroglia; Neuroprotective Agents; Phosphodiesterase Inhibitors; Potassium; Purinergic P1 Receptor Antagonists; Rats; Rats, Sprague-Dawley; Theophylline; Xanthines

Binding to adenosine A1 receptors and the status of their coupling to G proteins were studied in the hippocampus and parahippocampal gyrus of Alzheimer individuals and age-matched controls. The binding to A1 receptors was compared with binding to the N-methyl-D-aspartate receptor complex channel-associated sites (labeled with (+)-[3H]5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine maleate). In vitro quantitative autoradiography demonstrated a similar anatomical distribution of A1 receptors labeled either with an agonist ((-)-[3H]phenylisopropyladenosine) or antagonist ([3H]8-cyclopentyl-1,3-dipropylxanthine) in the brains of elderly controls. In Alzheimer patients, significant decreases in the density of both agonist and antagonist binding sites were found in the molecular layer of the dentate gyrus. Decreased A1 agonist binding was also observed in the CA1 stratum oriens and outer layers of the parahippocampal gyrus, while reduced antagonist binding was found in the subiculum and CA3 region. Reduced density of the N-methyl-D-aspartate receptor channel sites was found in the CA1 region and parahippocampal gyrus. The reductions in binding to adenosine A1 and N-methyl-D-aspartate receptors were due to a decrease in the density of binding sites (Bmax), and not changes in receptor affinity (KD). In both elderly control and Alzheimer subjects, GTP substantially reduced the density of A1 agonist binding sites with a concomitant increase in the KD values, whereas antagonist binding was unaffected by GTP. The results suggest that adenosine A1 receptor agonists and antagonists recognize overlapping populations of binding sites. Reduced density of A1 receptors in the molecular layer of the dentate gyrus most probably reflects damage of the perforant path input in Alzheimer's disease, while altered binding in the CA1 and CA3 regions is probably due to loss of intrinsic neurons. Similar effects of GTP on binding to A1 receptors in control and Alzheimer individuals suggest lack of alterations in coupling of A1 receptors to G proteins in Alzheimer's disease, thus supporting the notion of normal receptor coupling to their effector systems in Alzheimer's disease.

Topics: Adenosine; Aged; Aged, 80 and over; Alzheimer Disease; Autoradiography; Dizocilpine Maleate; Female; GTP-Binding Proteins; Hippocampus; Humans; Kinetics; Male; Organ Specificity; Pyramidal Tracts; Receptors, N-Methyl-D-Aspartate; Receptors, Purinergic; Tritium; Xanthines

The effects of adenosinergic antagonists caffeine and DPCPX, and of the adenosinergic agonists L-PIA, CPA and CGS 21680 were investigated on fully and partially reversible hypoxia-induced electrophysiological changes in rat hippocampal slices. The influence of a high potassium solution and of the N-methyl-D-aspartate antagonist dizocilpine (MK 801) was also tested. The latency to obtain a 50% decrease in the amplitude of the CA1 population spike (CA1 PS) during a short- (5-10 min) lasting hypoxic period was significantly increased (P less than 0.01) by slice perfusion with caffeine (50 microM), DPCPX (0.2 microM), and by increasing (from 3 to 4 mM) the potassium concentration in the medium bathing the hippocampal slices. The latency was significantly decreased (P less than 0.01) by slice perfusion with L-PIA (0.2 microM) and CPA (0.05 microM). It was not significantly modified by CGS 21680 (5 microM). The incidence of reappearance of the CA1 PS during reoxygenation after long- (45 min) lasting hypoxia was significantly increased (P less than 0.05) by slice perfusion with MK 801 (50 microM), while it was not significantly affected by slice perfusion with caffeine (50 microM) or DPCPX (0.2 microM) or L-PIA (0.2 microM) or CPA (0.05 microM) or CGS 21680 (5 microM). The results indicate a prevalent involvement of the A1 adenosine receptors in the early mechanisms underlying hypoxia-induced reversible changes. Adenosine seems to have a limited role in the late mechanisms occurring after a long-lasting hypoxic period.

Topics: Adenosine; Animals; Caffeine; Dizocilpine Maleate; Electrophysiology; Hippocampus; Hypoxia; In Vitro Techniques; Male; Membrane Potentials; Phenethylamines; Phenylisopropyladenosine; Potassium; Purinergic Antagonists; Rats; Rats, Inbred Strains; Synapses; Xanthines