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Differential effects of selective adenosine A1 and A2A receptor agonists on dopamine receptor agonist-induced behavioural responses in rats

1998; Elsevier BV; Volume: 347; Issue: 2-3 Linguagem: Inglês

10.1016/s0014-2999(98)00107-1

1879-0712

Roberto Rimondini, Sergi Ferré, Lydia Giménez‐Llort, Sven Ove Ögren, Kjell Fuxé,

Neurotransmitter Receptor Influence on Behavior

The effects of the systemic (i.p.) administration of the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the selective adenosine A2A receptor agonist sodium 2-p-carboxyethyl)phenylamino-5′-N-carboxamidoadenosine (CGS 21680) on different dopamine receptor agonist-induced behaviours were studied in the male rat. CGS 21680 (1 μmol/kg), but not CPA, was found to counteract the stereotypies induced by the non-selective dopamine receptor agonist apomorphine (0.25 mg/kg s.c.). Low doses of CGS 21680 (0.1 μmol/kg) and high doses of CPA (3 μmol/kg) counteracted yawning induced by the dopamine D2 selective agonist quinpirole (0.05 mg/kg). On the other hand, low doses of CPA (0.3 μmol/kg) antagonized grooming induced by the selective dopamine D1 receptor-selective agonist SKF 38393 (10 mg/kg i.p.), while CGS 21680 was ineffective. These results are consistent with the proposed existence of a selective antagonistic modulation of dopamine D1 and D2 receptors by adenosine A1 and A2A receptors, respectively. The ability of CGS 21680 to counteract apomorphine-induced stereotypies is weaker compared to its previously reported antagonistic effect of amphetamine-induced motor activity. This supports the hypothesis that adenosine A2A receptor agonists may be potential antipsychotic drugs with a low potential for extrapyramidal side effects.