Localization of adenosine A_2A-receptors in rat brain with [³H]ZM-241385

Abstract.

Adenosine plays a key role in the regulation of tissue oxygenation, neuronal firing, and neurotransmitter release. Four receptor subtypes have been identified and cloned: A₁, A_2A, A_2B, and A₃, although only A₁ and A_2A receptors are prominent in rat brain. Much evidence now indicates that A_2A receptors (A_2AR) are highly enriched within striatal medium-sized spiny GABAergic neurons where they are closely associated with, and modulate, D₂-dopaminergic receptors involved in motor control and reward behaviors. There is also consensus that A_2AR are present in the nucleus accumbens and olfactory tubercle where they have been postulated to interact with prostaglandins in the regulation of sleep. There is less agreement as to whether or not A_2AR are present in other brain regions. The present study describes an autoradiographic procedure that utilizes [³H]ZM-241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-α][1,3,5]triazin-5-ylamino]ethyl)phenol), a highly selective A_2A-receptor ligand. Saturable specific binding was found in the rat caudate putamen with a K _d=1.1 nM and B _max=1150 fmol/mg. Binding was also found in the nucleus accumbens and the olfactory tubercle, but was not detected in extra-striatal brain regions.