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Enhanced role of adenosine A 2A receptors in the modulation of LTP in the rat hippocampus upon ageing
Author(s) -
Costenla Ana R.,
Diógenes Maria J.,
Canas Paula M.,
Rodrigues Ricardo J.,
Nogueira Célia,
Maroco João,
Agostinho Paula M.,
Ribeiro Joaquim A.,
Cunha Rodrigo A.,
de Mendonça Alexandre
Publication year - 2011
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2011.07719.x
Subject(s) - long term potentiation , hippocampus , hippocampal formation , medicine , endocrinology , glutamate receptor , nmda receptor , ageing , neurotransmission , antagonist , neuroscience , synaptic plasticity , psychology , chemistry , receptor
Adenosine neuromodulation depends on a balanced activation of inhibitory A 1 (A 1 R) and facilitatory A 2A receptors (A 2A R). Both A 1 R and A 2A R modulate hippocampal glutamate release and NMDA‐dependent long‐term potentiation (LTP) but ageing affects the density of both A 1 R and A 2A R. We tested the effects of selective A 1 R and A 2A R antagonists in the modulation of synaptic transmission and plasticity in rat hippocampal slices from three age groups (young adults, 2–3 month; middle‐aged adults, 6–8 months; aged, 18–20 months). The selective A 2A R antagonist SCH58261 (50 n m ) attenuated LTP in all age groups, with a larger effect in aged (−63 ± 7%) than in middle‐aged adults (−36 ± 9%) or young adult rats (−36 ± 9%). In contrast, the selective A 1 R antagonist DPCPX (50 n m ) increased LTP magnitude in young adult rats (+42 ± 6%), but failed to affect LTP magnitude in the other age groups. Finally, in the continuous presence of DPCPX, SCH58261 caused a significantly larger inhibition of LTP amplitude in aged (−71 ± 45%) than middle‐aged (−28 ± 9%) or young rats (−11 ± 2%). Accordingly, aged rats displayed an increased expression of A 2A R mRNA in the hippocampus and a higher number of glutamatergic nerve terminals equipped with A 2A R in aged (67 ± 6%) compared with middle‐aged (34 ± 7%) and young rats (25 ± 5%). The results show an enhanced A 2A R‐mediated modulation of LTP in aged rats, in accordance with the age‐associated increased expression and density of A 2A R in glutamatergic terminals. This age‐associated gain of function of A 2A R modulating synaptic plasticity may underlie the ability of A 2A R antagonists to prevent memory dysfunction in aged animals.