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Modification of adenosine modulation of synaptic transmission in the hippocampus of aged rats
Author(s) -
Sebastião A M,
Cunha R A,
De Mendonça A,
Ribeiro J A
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703736
Subject(s) - adenosine a1 receptor , adenosine , neurotransmission , medicine , endocrinology , agonist , adenosine deaminase , adenosine receptor , adenosine a3 receptor , hippocampus , inhibitory postsynaptic potential , chemistry , receptor , biology
We compared the modulation of synaptic transmission by adenosine A 1 receptors in the hippocampus of aged (24 months) and young adult rats (6 weeks). The adenosine A 1 receptor agonist, N 6 ‐cyclopentyladenosine, was less potent ( P <0.05) to inhibit synaptic transmission in aged (EC 50 =53 n M ) than young adult (EC 50 =14 n M ) hippocampal slices, these effects being prevented by the A 1 receptor antagonist, 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX). In contrast with the lower effect of the A 1 receptor agonist, it was observed that blockade of A 1 receptors with DPCPX (50 n M ), or removal of endogenous extracellular adenosine with adenosine deaminase (2 u ml −1 ), caused a more pronounced disinhibition of synaptic transmission in aged rats. Also consistent with a more intense A 1 receptor‐mediated inhibitory tonus by endogenous adenosine in aged rats was the finding that to fully prevent the depression of synaptic transmission induced by 3 min hypoxia, a higher concentration of DPCPX was required in slices from aged (100 n M ) than from young (50 n M ) rats. It is concluded that in hippocampal slices of aged rats the efficiency of A 1 receptors to modulate synaptic transmission is reduced, but this may be compensated by an enhanced inhibitory tonus by endogenous adenosine.British Journal of Pharmacology (2000) 131 , 1629–1634; doi: 10.1038/sj.bjp.0703736