AbstractWe previously reported that adenosine, through A2A receptor activation, potentiates synaptic actions of brain‐derived neurotrophic factor (BDNF) in the hippocampus of infant (3–4 weeks) rats. Since A2A‐receptor‐mediated actions are more evident in old than in young rats and since the therapeutic potential for BDNF‐based strategies is greater in old subjects, we now evaluated synaptic actions of BDNF and the levels of TrkB receptors and of adenosine A2A receptors in the hippocampus of three groups of adult rats: young adults (10–16 weeks), old adults (36–38 weeks), and aged (70–80 weeks), as well as in one group of infant (3–4 weeks) rats. BDNF (20 ng/ml) enhances field excitatory postsynaptic potentials recorded from the hippocampus of young adults and aged rats, an action triggered by adenosine A2A receptor activation, since it was blocked by the A2A receptor antagonist, ZM 241385. In the other groups of animals BDNF (20 ng/ml) was virtually devoid of action on synaptic transmission. Western blot analysis of receptor density shows decreased amounts of TrkB receptors in old adults and aged rats, whereas A2A receptor levels assayed by ligand binding are enhanced in the hippocampus of old adults and aged rats. It is concluded that age‐related changes in the density of TrkB receptors and of adenosine A2A receptors may be responsible for a nonmonotonous variation of BDNF actions on synaptic transmission in the hippocampus. © 2007 Wiley‐Liss, Inc.