Figure 8:  Dopamine - ADO interactions in the basal ganglia.

An indirect pathway dopaminergic pathway arises from the striatal GABA - enkephalinergic dopaminergic neurons (striatopallidal system) on which both dopamine D2 and ADO A2A receptors are co-localized. Via a GABAergic interneuron originating in the external globus pallidus, the indirect pathway connects with a glutaminergic pathway arising in the subthalamic nucleus. This, in turn can activate the internal segment of the pars reticulata and through another GABA pathway inhibits ascending glutaminegic neurons arising from the thalamus that innervate the cortex. The direct pathway arises from striatal GABA - Substance P - dynorphinergic neurons (striatonigral-striatoentopeduncular system) that via a GABAergic relay inhibit the internal segment of the pars reticulata to disinhibit the ascending thalamic/ cortical glutaminergic pathway. The balance between the direct (activating) and indirect (inhibitory) striatal dopaminergic pathways can then tonically regulate normal motor activity. Dopaminergic inputs arising from the substantia nigra pars compacta can faciltate motor activity, inhibiting the indirect pathway by activation of D2 receptors and activating the direct pathway via D1 receptor activation.  Activation of either A2A receptors (indirect pathway) or A1 receptors (direct pathway) can mimic the effects of D2 or D1 receptor antagonists, respectively.  (adapted from 30 and 75).

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published 2000