Adenosine A(1) receptor-dopamine D-1 receptor interaction in the rat limbic system: Modulation of dopamine D-1 receptor antagonist binding sites

Antagonistic interactions between adenosine A(2a) and dopamine D-2 receptors and between adenosine A(1) and dopamine D-1 receptors have been previously found in the basal ganglia. Those interactions have been proposed to be key mechanisms of action responsible for the motor depressant effects of adenosine agonists and the motor activating effects of adenosine antagonists, like caffeine. By using quantitative receptor autoradiography, the selective adenosine A(1) receptor agonist N-6-cyclopentyladenosine was found to decrease the affinity of dopamine D-1 receptors for the specific D-1 antagonist [I-125]SCH 23982 in both the nucleus accumbens and the medial prefrontal cortex of the rat brain. The present results suggest that dopamine neurotransmission, through an A(1)-D-1 interaction, might also be involved in the behavioural effects of adenosine agonists and antagonists not related to motor activity, like the sedative-hypnogenic properties of adenosine analogues and the psychostimulant effects of caffeine.