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B. B. FREDHOLM ANAL. REAL ACAD. NAL. FARM.

Interestingly, the levels of adenosine A1 receptor mRNA and protein are
differently regulated by, e.g., long term antagonist treatment (Johansson,
Ahlberg, van der Ploeg, Brené, Lindefors, Persson and Fredholm; 1993)
and during development (Ådén, Herlenius, Tang and Fredholm; 2000).
The general distribution of adenosine A1 receptors is similar between
rodents and humans (Fastbom, Pazos and Palacios; 1987, Svenningsson,
Hall, Sedvall and Fredholm; 1997, Schindler, Harris, Hayes, Papotti and
Humphrey; 2001). Initial attempts to localize adenosine A1 receptors in
the living brain using [11C]KF15372 and [11C]MPDX and positron
emission tomography (PET) have been made (Noguchi, Ishiwata, Furuta,
Simada, Kiyosawa, Ishii, Endo, Suzuki and Senda; 1997, Shimada,
Ishiwata, Kiyosawa, Nariai, Oda, Toyama, Suzuki, Ono and Senda;
2002).

Adenosine A2A receptor mRNA is highly enriched in the striatum
(Schiffmann, Libert, Vassart and Vanderhaeghen; 1991, Fink, Weaver,
Rivkees, Peterfreund, Pollack, Adler and Reppert; 1992, Svenningsson,
Hall, Sedvall and Fredholm; 1997). Lower levels are also found in
extrastriatal areas, such as lateral septum, cerebellum, cortex and
hippocampus (Dixon, Gubitz, Sirinathsinghji, Richardson and Freeman;
1996, Svenningsson, Hall, Sedvall and Fredholm; 1997). Most striatal
neurons (95%) are GABAergic projection neurons. These neurons can be
divided into two major subtypes based on their target areas and
neuropeptide contents. One sub-population projects to globus pallidus and
contain enkephalin. Another sub-population projects to substantia nigra
pars reticulata/the entopeduncular nucleus and contains substance P and
dynorphin. Interestingly, adenosine A2A receptors are selectively
expressed in the enkephalin-containing striatopallidal neurons
(Schiffmann, Libert, Vassart and Vanderhaeghen; 1991, Fink et al.; 1992,
Augood and Emson; 1994, Svenningsson, Hall, Sedvall and Fredholm;
1997). In addition to the GABAergic projection neurons, there are also
cholinergic and GABAergic interneurons in striatum. It is still
controversial whether these interneurons contain adenosine A2A receptors.
Studies using in situ hybridization have been unable to detect adenosine
A2A receptor mRNA in interneurons (Schiffmann, Libert, Vassart and
Vanderhaeghen; 1991, Augood and Emson; 1994, Svenningsson, Hall,
Sedvall and Fredholm; 1997). However, a single cell PCR study detected

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