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Age-related changes of A1 and A2a adenosine receptor binding characteristics were investigated in three regions of the rat brain using the A1 selective antagonist 3HDPCPX, and the A2a selective agonist 3HCGS 21680. The density of A1 binding sites in aged rats (24 months) was decreased by 33% in the hippocampus and by 60% in the cortex and was unchanged in the striatum when compared with young adult rats (6 weeks), with no change in KD. There were also age-related changes in the density of A2a binding sites: in the cortex, there was a 94% increase in the number of 3HCGS 21680 binding sites in aged rats compared with young rats, and a similar tendency was observed in the hippocampus (32% increase in A2a binding sites in aged rats), with no change in KD; in the striatum there was a tendency for a decrease (22%) in the number of 3HCGS 21680 binding sites in aged rats, and a decrease in KD. These results suggest that there are age-related changes in the balance between inhibitory A1- and excitatory A2a-adenosine receptor-mediated actions, which vary in different brain areas: in the cortex and hippocampus, the balance might be shifted towards adenosine-mediated excitatory actions, since there is an increase in the number of A2a receptors and a decrease in the number of A1 receptors upon ageing. In contrast, in the striatum, the A1/A2a ratio might be only slightly affected upon ageing.
Cunha et al. (Sat,) studied this question.