Schizophrenia

Adenosine A2A receptors are highly enriched in the basal ganglia, where they are present in highest abundance on a subset of the GABAergic output neurons, namely those that project to the globus pallidus (Schiffmann etal. 1991; Fink etal. 1992; Svenningsson etal. 1997; Rosin etal. 1998). These neurons also express dopamine D2 receptors and it is abundantly clear that the two receptors interact in binding assays (Ferré et al. 1991), on signal transduction (Kull et al. 1999), and behaviourally (Fink et al. 1992; Fredholm et al. 1999; Svenningsson et al. 1999b). It appears that one major role of dopamine in the striatum is to suppress signaling via A2a receptors (Svenningsson etal. 1999a; Chen etal. 2001). Given that antagonists ofD2 receptors are used in the treatment of schizophrenia, there are interesting implications for the pathophysiology of that disease and/or its treatment. When tonic adenosine A2a receptor activation is unopposed by dopamine for a long period of time, the response to adenosine receptor stimulation decreases (Zahniser etal. 2000), even though significant effects remain (Chen etal. 2001).

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