Selective adenosine A(2A) receptor dopamine D-2 receptor interactions in animal models of schizophrenia

In the apomorphine-induced climbing mouse assay, the potencies of the selective adenosine A(1) receptor agonist, N-6-cyclohexyladenosine (CHA), and the selective A(2A) adenosine receptor agonist, 2-p-(2-carboxyethyl) phenethylamino 5'-N-ethylcarboxamidoadenosine (CGS 21680), and various dopamine receptor antagonists were as follows: SCH 23390 = haloperidol > raclopride > CHA = CGS 21680. While in catalepsy, their potencies were SCH 23390 > haloperidol. raclopride > CGS 21680. CHA failed to induce catalepsy due to significant sedation/ataxia. The combined administration of the ED(15) dose of CHA failed to potentiate the ED(50) value of SCH 23390, raclopride, or haloperidol in the apomorphine-induced climbing mouse assay. However, the combined administration of the ED(15) dose of CGS 21680 significantly decreased the ED(50) of raclopride by 8.0-fold and haloperidol by 35-fold. The adenosine A(2A) receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), significantly decreased catalepsy induced by raclopride and haloperidol, while the adenosine A(1) receptor antagonist, 1,3-dimethyl-8-phenylxanthine (8-PT), was ineffective. The present results show that in behavioral assays predictive for antipsychotic activity, adenosine receptor agonists block behaviors in a similar manner to dopamine receptor antagonists.