Distribution and postnatal ontogeny of adenosine A 2A receptors in rat brain: comparison with dopamine receptors

Abstract

In adult rat brain, adenosine A 2A receptors and dopamine D 2 receptors are known to be located on the same cells where they interact in an antagonistic manner. In the present study we wanted to examine when this situation develops and compared the postnatal ontogeny of the binding of the adenosine A 2A receptor agonist [ 3H]CGS 21680, the binding of the dopamine D 1 receptor antagonist [ 3H]SCH 23390 and the dopamine D 2 receptor antagonist [ 3H]raclopride. All three radioligands bound to the striatum at birth and this binding increased several-fold during the postnatal period. [ 3H]SCH 23390 binding developed first (mostly during the first week), followed by [ 3H]raclopride binding (first to third week) and [ 3H]CGS 21680 binding (only during second and third week). For all three radioligands the binding tended to decrease between 21 days and adulthood. This occurred earlier and was more pronounced in the globus pallidus than in the other examined structures. The increase in [ 3H]CGS 21680 binding from newborn to adult was mainly due to four-fold increase in the number of binding sites. The pharmacology of [ 3H]CGS 21680 binding to caudate–putamen was similar in newborn, one-week-old and adult animals, and was indicative of A 2A receptors. The binding was inhibited by guanylyl imidodiphosphate at all ages, indicating that A 2A receptors are G-protein-coupled already at birth. In contrast to the large increase in [ 3H]CGS 21680 binding, there was a decrease in the levels of A 2A messenger RNA during the postnatal period in the caudate–putamen. In cerebral cortex [ 3H]CGS 21680 bound to a different site than the A 2A receptor. From birth to adulthood cortical binding of [ 3H]CGS 21680 increased four-fold and that of the adenosine A 1 agonist [ 3H]cyclohexyladenosine 19-fold. During early postnatal development [ 3H]SCH 23390 binding was higher in deep than in superficial cortical layers, but this difference disappeared in adult animals. There was binding of both [ 3H]CGS 21680 and [ 3H]cyclohexyladenosine to the olfactory bulb, suggesting a role of the two adenosine receptors in processing of olfactory information. [ 3H]CGS 21680 binding was present in the external plexiform layer and glomerular layer, and increased during development, but the density of binding sites was about one tenth of that seen in caudate–putamen. [ 3H]cyclohexyladenosine showed a very different labelling pattern, resembling that observed with [ 3H]SCH 23390. Postnatal changes in adenosine receptors may explain age-dependent differences in stimulatory caffeine effects and endogenous protection against seizures. Since A 2A receptors show a co-distribution with D 2 receptors throughout development, caffeine may partly exert such actions by regulating the activity of D 2 receptor-containing striatopallidal neurons