Behavioral control by striatal adenosine A2A ‐dopamine D2 receptor heteromers

G protein‐coupled receptors (GPCR) exhibit the ability to form receptor complexes that include molecularly different GPCR (ie, GPCR heteromers), which endow them with singular functional and pharmacological characteristics. The relative expression of GPCR heteromers remains a matter of intense debate. Recent studies support that adenosine A2A receptors (A2AR) and dopamine D2 receptors (D2R) predominantly form A2AR‐D2R heteromers in the striatum. The aim of the present study was evaluating the behavioral effects of pharmacological manipulation and genetic blockade of A2AR and D2R within the frame of such a predominant striatal heteromeric population. First, in order to avoid possible strain‐related differences, a new D2R‐deficient mouse with the same genetic background (CD‐1) than the A2AR knock‐out mouse was generated. Locomotor activity, pre‐pulse inhibition (PPI) and drug‐induced catalepsy were then evaluated in wild‐type, A2AR and D2R knock‐out mice, with and without the concomitant administration of either the D2R agonist sumanirole or the A2AR antagonist SCH442416. SCH442416‐mediated locomotor effects were demonstrated to be dependent on D2R signaling. Similarly, a significant dependence on A2AR signaling was observed for PPI and for haloperidol‐induced catalepsy. The results could be explained by the existence of one main population of striatal postsynaptic A2AR‐D2R heteromers, which may constitute a relevant target for the treatment of Parkins...
Source: Genes, Brain and Behavior - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research