Adenosine modulates synaptic plasticity in hippocampal slices from aged rats

Abstract

Adenosine is known to modulate synaptic plasticity in the hippocampus of young animals through activation of adenosine A 1 receptors. The objective of the present study is to investigate whether the modulatory role of adenosine on phenomena of synaptic plasticity is maintained or modified in the hippocampus of aged animals. We compared the effects of the selective adenosine A 1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50 nM), on paired-pulse facilitation (PPF), long-term depression (LTD), long-term potentiation (LTP) and depotentiation elicited in hippocampal slices taken from young adult (5–6 weeks) and old (2 years old) male Wistar rats. DPCPX attenuated PPF both in young (1.64±0.05 vs. 1.76±0.05%, n=6) and in old rats (1.33±0.05 vs. 1.55±0.1%, n=6). LTD was only observed in the presence of DPCPX in both young (21.3±0.6%, n=4) and old rats (14.4±0.9%, n=6). LTP induced by high-frequency stimulation (HFS) was not significantly different in young and old animals, in the presence or in the absence of DPCPX. A larger depotentiation was observed in the presence of DPCPX in young rats (27.6±4.4% vs. 16.8±4.7%, n=7) as well as in old rats (41.3±5.1% vs. 16.1±2.7%, n=6). LTP induced by θ-burst stimulation was observed only in the presence of DPCPX (53.9±4.9%, n=5) in young rats, but could be obtained either in the control solution (81.8±17.9%, n=7) or in the presence of DPCPX (98.5±24.2%, n=7) in old rats. The modulatory role of endogenous adenosine on synaptic plasticity is generally maintained in aged animals. Drugs interfering with adenosine A 1 receptor effects could then be used in old animals to modify synaptic plasticity with relevant behavioural consequences.