Genetic interdependence of adenosine and dopamine receptors: Evidence from receptor knockout mice

Abstract

Dopamine and adenosine receptors are known to share a considerable overlap in their regional distribution, being especially rich in the basal ganglia. Dopamine and adenosine receptors have been demonstrated to exhibit a parallel distribution on certain neuronal populations, and even when not directly co-localized, relationships (both antagonistic and synergistic) have been described. This study was designed to investigate dopaminergic and purinergic systems in mice with ablations of individual dopamine or adenosine receptors. In situ hybridization histochemistry and autoradiography was used to examine the level of mRNA and protein expression of specific receptors and transporters in dopaminergic pathways. Expression of the mRNA encoding the dopamine D 2 receptor was elevated in the caudate putamen of D 1, D 3 and A 2A receptor knockout mice; this was mirrored by an increase in D 2 receptor protein in D 1 and D 3 receptor knockout mice, but not in A 2A knockout mice. Dopamine D 1 receptor binding was decreased in the caudate putamen, nucleus accumbens, olfactory tubercle and ventral pallidum of D 2 receptor knockout mice. In substantia nigra pars compacta, dopamine transporter mRNA expression was dramatically decreased in D 3 receptor knockout mice, but elevated in A 2A receptor knockout mice. All dopamine receptor knockout mice examined exhibited increased A 2A receptor binding in the caudate putamen, nucleus accumbens and olfactory tubercle. These data are consistent with the existence of functional interactions between dopaminergic and purinergic systems in these reward and motor-related brain regions.