Antagonistic interaction between adenosine A2A and dopamine D2 receptors modulates the social recognition memory in reserpine-treated rats.
Increasing evidence suggests that antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia are involved in the control of motor activity. However, there are few studies investigating this interaction in other brain regions and its role in additional functions. In the present study, we evaluated whether reserpine-treated rats (1.0 mg/kg, i.p.) exhibit altered social recognition memory abilities. The effects of acute administration of the dopamine receptor agonists 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine (SKF 38393, dopamine D(1) receptor agonist) and quinpirole (dopamine D(2) receptor agonist), together with the adenosine receptor antagonists caffeine (non-selective), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, adenosine A(1) receptor antagonist) and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, adenosine A(2A) receptor antagonist), were also investigated. Twenty-four hours after treatment, reserpine-treated rats exhibited a significant disruption in the ability to recognize a juvenile rat after a short period of time. These animals did not show any motor deficit. The social recognition disruption induced by reserpine was reversed by acute treatment with quinpirole (0.05-0.1 mg/kg, i.p.), caffeine (10.0-30.0 mg/kg, i.p.) or ZM241385 (0.5-1.0 mg/kg, i.p.), but not with SKF 38393 (0.5-3.0 mg/kg, i.p.) or DPCPX (0.5-3.0 mg/kg, i.p.). Moreover, a synergistic response was observed following the co-administration of 'non-effective' doses of ZM241385 (0.1 mg/kg, i.p.) and quinpirole (0.01 mg/kg, i.p.). These results reinforce and extend the notion of antagonistic interactions between adenosine and dopamine receptors, and demonstrate, for the first time, that the blockade of adenosine A(2A) receptors and the activation of dopamine D(2) receptors can reverse the social recognition deficits induced by reserpine in rats.
Prediger
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Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis-SC, Brazil.
Da Cunha
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Takahashi
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D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D007274:Injections, Intraperitoneal; D008297:Male; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects*; D021641:Recognition, Psychology / Q000187:drug effects*; D012110:Reserpine / Q000008:administration & dosage / Q000494:pharmacology*; D012919:Social Behavior
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D012110:Reserpine