Elsevier

Neuropharmacology

Volume 36, Issue 2, February 1997, Pages 161-167
Neuropharmacology

Endogenous Adenosine Attenuates Long-term Depression and Depotentiation in the CA1 Region of the Rat Hippocampus

https://doi.org/10.1016/S0028-3908(96)00173-6Get rights and content

Abstract

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. © 1997 Elsevier Science Ltd. All rights reserved.

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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