Endogenous Adenosine Attenuates Long-term Depression and Depotentiation in the CA1 Region of the Rat Hippocampus
Section snippets
MATERIALS AND METHODS
The experiments were performed on hippocampal slices taken from young (12–14-day old) Wistar rats. The animals were anesthetized with halothane, decapitated, and the right hippocampus dissected free, within an ice-cold artificial cerebrospinal fluid (aCSF) of the following composition (mM): NaCl 124, KCl 3, NaH2PO4 1.25, NaHCO3 26, MgSO4 1, CaCl2 2, glucose 10, and gassed with a 95% O2 + 5% CO2 mixture. Slices (400 μm thick) were cut perpendicularly to the long axis of the hippocampus with a
Characterization of long-term depression and depotentiation
When LFS was applied in one pathway (S1) in the presence of the NMDA receptor antagonist, dl-2-amino-5-phosphonopentanoate (AP5; 50 μM, allowed to equilibrate for at least 30 min), a small value for LTD, 11.9 ± 5.6 decrease in fepsp slope (n = 4) was obtained. In contrast, after washing out the NMDA receptor antagonist for about 40 min (and without resetting stimulus intensity) LFS re-applied in the same pathway elicited a much larger LTD, 31.0 ± 3.1 decrease in fepsp slope (p < 0.05).
DISCUSSION
The main result of the present work is that endogenous adenosine limits long-term depression and depotentiation in the hippocampus through the activation of adenosine A1 receptors, as evaluated by the facilitation of both LTD and depotentiation in the presence of the selective adenosine A1 receptor antagonist, DPCPX (10 nM). The concentration of DPCPX (10 nM) used in the present study was four times the concentration that has previously been shown to antagonize completely the inhibitory
Acknowledgements
We are grateful to the deceased Dr Maria José de Mendonça for organization of the bibliography database. A. de M. thanks Professor A. Castro Caldas for encouragement. This work was supported by Gulbenkian Foundation, JNICT and EU. A. de M. and J.A.R. are involved in an EU concerted action (Biomed I/ADEURO).
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