Page 129 - 69_04

VOL. 69 (4) ADENOSINE RECEPTORS

adenosine A2A receptor mRNA in cholinergic interneurons (Richardson,
Dixon, Lee, Bell, Cox, Williams, Pinnock and Freeman; 2000).

Studies using immunohistochemistry and ligand autoradiography
show high levels of adenosine A2A receptors in all sub-regions of striatum
(Jarvis and Williams; 1988, Parkinson and Fredholm; 1990, Rosin et al.;
1998). In addition, high levels of adenosine A2A receptors have also been
found in globus pallidus. These receptors are located on nerve terminals
from the striatal projection neurons which innervate globus pallidus
(Rosin et al.; 1998). Using A2A receptor-selective antibodies and
immunohistochemistry at the light- and electron-microscopic levels,
Rosin and her colleagues (Rosin et al.; 1998, Hettinger et al.; 2001) have
shown that striatal adenosine A2A receptors are found in most neuronal
compartments, i.e. dendrites, terminals of axon collaterals and in soma.
However, the highest levels are found in dendrites and dendritic spines
that form asymmetric synapses. These synapses receive input from
glutamatergic terminals and are of excitatory nature. This postsynaptic
localization of A2A receptors implies that A2A receptors may play an
important role in the regulation of synaptic plasticity. Indeed, a functional
correlate to this anatomical finding has recently been demonstrated,
namely that NMDA receptor-dependent long-term potentiation in the
nucleus accumbens is significantly attenuated by selective A2A receptor
antagonists or in A2A receptor KO mice (d'Alcantara, Ledent, Swillens
and Schiffmann; 2001).

The distribution of adenosine A2A receptors is similar in rodents
and humans (Martinez-Mir, Probst and Palacios; 1991, Schiffmann,
Libert, Vassart and Vanderhaeghen; 1991). However, the levels of
extrastriatal adenosine A2A receptors appear to be higher in humans than
in rodents. Since there is accumulating evidence for a critical role of
adenosine A2A receptors in the pathophysiology of several neurological
and psychiatric disorders, most notably Parkinson’s disease and
schizophrenia, it will be of great interest to be able to monitor the levels
of adenosine A2A receptors in the living brain using PET. There are
several reports about various ligands, including [11C]KW-6002, [11C]IS-
DMPX, [11C]KF 18446 and [11C]KF 17837 (Stone-Elander, Thorell,
Eriksson, Fredholm and Ingvar; 1997, Ishiwata, Noguchi, Wakabayashi,

143