Strain-related differences in adenosine receptor density and in behavioral sensitivity to adenosine analogs in mice

The behavioral effects of the adenosine agonists 5'-N-ethylcarboxamidoadenosine (NECA) was investigated in two strains of inbred mice, CD1 and CBA. NECA dose dependently reduced spontaneous locomotor activity with similar potency (ED50 = 36 +/- 1.5 and 36 +/- 1.1 nmol/kg IP for CBA and CD1 mice, respectively) and efficacy (> 90% at 100 nmol/kg) in the two strains. One nmol/kg NECA, an ineffective dose in CBA mice, exerted a significant stimulant action in CD1 mice. In saturation experiments, no differences were found in the density or in the affinity of striatal A2a receptors labeled with [3H]NECA. A strain-related difference was found in the density of striatal A1 receptors labeled with [3H]CCPA. In CBA mice, the Bmax value was 32% less than in CD1 mice (0.646 +/- 0.037 and 0.951 +/- 0.073 pmol bound/mg protein, respectively, p < 0.05). No differences in [3H]CCPA binding parameters were found in cortical and hippocampal membranes obtained from the two strains, whereas a higher density of A1 binding sites was found in the cerebellum of CBA mice. The present results show a close correlation between binding studies and the depressant action of NECA and present evidence for strain-related differences in regional distribution of central adenosine receptors and in behavioral response to purinergic drugs.