The nucleus accumbens is a brain region involved in motivation, attention, reward and drug addiction. The output of this area is determined by the bursting activity in the medium-sized spiny GABAergic neurons (MSN), which is central to basal ganglia function and dysfunction. These bursts are driven by multiple corticostriatal inputs that depolarize MSN from their resting hyperpolarized membrane potential around -80 mV, which is recognized as the down-state, to a more depolarized level near -55 mV, called the up-state. These transitions between down- and up-state require channels regulated by several striatal transmitters acting through G protein coupled receptors. These transmitters are therefore in position to tightly control the excitability and firing patterns of the MSN. Among these neurons, enkephalin and dopamine D₂ receptor-expressing neurons are highly enriched in adenosine A_2A receptor. This co-expression of the D₂ and A_2A receptors supports strong interactions between them but their physiological significance at the cellular level remains partially unclear.

In the present study, perforated patch clamp recordings on acute rat brain slices were performed to characterize the role of D₂-A_2A receptors interactions in the neuromodulation of transitions between down- and up -state by using the D₂ receptor agonist norapomorphine (NPA) and the A_2A receptor agonist CGS 21680.