ADENOSINE-DOPAMINE INTERACTIONS IN THE VENTRAL STRIATUM - IMPLICATIONS FOR THE TREATMENT OF SCHIZOPHRENIA

The ventral striatum is included in brain circuits which connect brain areas classically ascribed to the motor or to the limbic system. In f act, the ventral striatum is involved in the connection between motiva tionally relevant stimuli and adaptive behaviours. Dopamine neurotrans mission 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 pro duce similar behaviour-al effects as dopamine antagonists. On the othe r hand, adenosine antagonists, like caffeine? produce similar effects to increased dopaminergic neurotransmission in the striatum. Specific antagonistic interactions between specific subtypes of adenosine and d opamine receptors in the basal ganglia play an essential role in the b ehavioural effects of adenosine agonists and antagonists. III particul ar, a strong antagonistic interaction between adenosine A(2A) and dopa mine D-2 receptors seems to take place in the striopallidal GABAergic neurons which originate in the ventral striatum. Therefore, adenosine A(2)A agonists provide a potential new treatment for schizophrenia, si nce the dopamine D-2 receptors of the ventral striopallidal neurons ap pear to be involved in the antipsychotic effects of neuroleptics. In f act: in animal models, the adenosine A(2)A agonist CGS 21680 has a pro file of antipsychotic with a low liability to induce extrapyramidal si de effects.