DISTRIBUTION AND POSTNATAL ONTOGENY OF ADENOSINE A(2A) RECEPTORS IN RAT-BRAIN - COMPARISON WITH DOPAMINE-RECEPTORS

In adult rat brain, adenosine A(2A) receptors and dopamine D-2 recepto rs 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 t his situation develops and compared the postnatal ontogeny of the bind ing of the adenosine A(2A) receptor agonist [H-3]CGS 21680, the bindin g of the dopamine D-2 receptor antagonist [H-3]SCH 23390 and the dopam ine D-2 receptor antagonist [H-3]raclopride. All three radioligands bo und to the striatum at birth and this binding increased several-fold d uring the postnatal period. [H-3]SCH 23390 binding developed first (mo stly during the first week), followed by [H-3]raclopride binding (firs t to third week) and [H-3]CGS 21680 binding (only during second and th ird week). For all three radioligands the binding tended to decrease b etween 21 days and adulthood. This occurred earlier and was more prono unced in the globus pallidus than in the other examined structures. Th e increase in [H-3]CGS 21680 binding from newborn to adult was mainly due to four-fold increase in the number of binding sites. The pharmaco logy of [H-3]CGS 21680 binding to caudate-putamen was similar in newbo rn, one-week-old and adult animals, and was indicative of A(2A) recept ors. The binding was inhibited by guanylyl imidodiphosphate al all age s, indicating that A(2A) receptors are G-protein-coupled already at bi rth. In contrast to the large increase in [H-3]CGS 21680 binding, ther e was a decrease in the levels of A(2A) messenger RNA during the postn atal period in the caudate-putamen. In cerebral cortex [H-3]CGS 21680 bound to a different site than the A(2A) receptor. From birth to adult hood cortical binding of [H-3]CGS 21680 increased four-fold and that o f the adenosine A(1) agonist [H-3]cyclohexyladenosine 19-fold. During early postnatal development [H-3]SCH 23390 binding was higher in deep than in superficial cortical layers, but this difference disappeared i n adult animals. There was binding of both [H-3]CGS 21680 and [H-3]cyc lohexyladenosine to the olfactory bulb, suggesting a role of the two a denosine receptors in processing of olfactory information. [H-3]CGS 21 680 binding was present in the external plexiform layer and glomerular layer, and increased during development, but the density of binding s ites was about one tenth of that seen in caudate-putamen. [H-3]cyclohe xyladenosine showed a very different labelling pattern, resembling tha t observed with [H-3]SCH 23390. Postnatal changes in adenosine recepto rs may explain age-dependent differences in stimulatory caffeine effec ts and endogenous protection against seizures. Since A(2A) receptors s how a co-distribution with D-2 receptors throughout development, caffe ine may partly exert such actions by regulating the activity of D-2 re ceptor-containing striatopallidal neurons. (C) 1997 IBRO. Published by Elsevier Science Ltd.