title: A role for extracellular adenosine in time-dependent reversal of long-term potentiation by low-frequency stimulation at hippocampal CA1 synapses.
abstract: The involvement of adenosine on the development of time-dependent reversal of long-term potentiation (LTP) by low-frequency stimulation (LFS) was investigated at Schaffer collateral-CA1 synapses of rat hippocampal slices. A train of LFS (2 Hz, 10 min, 1200 pulses) had no long-term effects on synaptic transmission but produced lasting depression of previously potentiated responses. This reversal of LTP (depotentiation) was observed when the stimulus was delivered </=3 min after induction of LTP. However, application at 10 min after induction had no detectable effect on potentiation. This time-dependent reversal of LTP by LFS appeared to be mediated by extracellular adenosine, because it was mimicked by bath-applied adenosine and was specifically inhibited by the selective A(1) adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM). The effect of adenosine could be mimicked by 5-HT(1A) receptor agonist buspirone, but the LFS-induced depotentiation could not be antagonized by 5-HT(1A) receptor antagonist NAN-190. The source of extracellular adenosine in response to LFS appeared to be attributable to the efflux of cAMP. In addition, this LFS-induced depotentiation was blocked by bath application of adenylyl cyclase activator forskolin or injection of a cAMP analog Sp-adenosine cAMP (10 mM) into postsynaptic neurons. Moreover, the selective protein phosphatase 1 and 2A inhibitors okadaic acid and calyculin A prevented the LFS-induced depotentiation. These results thus suggest that increasing extracellular adenosine appears to underlie the LFS-induced depotentiation via acting on the A(1) receptor subtype to interrupt the cAMP-dependent biochemical processes leading to the LTP expression.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan 70101.
authors.forename: C C
authors.initials: CC
authors.lastname: Huang
authors.forename: Y C
authors.initials: YC
authors.lastname: Liang
authors.forename: K S
authors.initials: KS
authors.lastname: Hsu
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D016018:Least-Squares Analysis; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D010879:Piperazines; D058915:Purinergic P1 Receptor Antagonists; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013873:Thionucleotides; D014970:Xanthines; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D000241:Adenosine; D013805:Theobromine; D002065:Buspirone