Adenosine-dopamine interactions in the ventral striatum Implications for the treatment of schizophrenia

Abstract

 The ventral striatum is included in brain circuits which connect brain areas classically ascribed to the motor or to the limbic system. In fact, the ventral striatum is involved in the connection between motivationally relevant stimuli and adaptive behaviours. Dopamine neurotransmission in the ventral striatum is essential for the increase in motor activity produced by motivational, salient, stimuli, such as food or novelty or by the administration of psychostimulants. Adenosine plays a role opposite to dopamine in the striatum and adenosine agonists produce similar behavioural effects as dopamine antagonists. On the other hand, adenosine antagonists, like caffeine, produce similar effects to increased dopaminergic neurotransmission in the striatum. Specific antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia play an essential role in the behavioural effects of adenosine agonists and antagonists. In particular, a strong antagonistic interaction between adenosine A_2A and dopamine D₂ receptors seems to take place in the striopallidal GABAergic neurons which originate in the ventral striatum. Therefore, adenosine A_2A agonists provide a potential new treatment for schizophrenia, since the dopamine D₂ receptors of the ventral striopallidal neurons appear to be involved in the antipsychotic effects of neuroleptics. In fact, in animal models, the adenosine A_2A agonist CGS 21680 has a profile of antipsychotic with a low liability to induce extrapyramidal side effects.