D1-dopamine and α1-adrenergic receptors co-localize in dendrites of the rat prefrontal cortex

• D1 dopamine and α1-adrenergic receptors co-localize in prefrontal cortex neurons.
• Amount of co-localization is greatest in dendrites.
• A greater fraction of α1-adrenergic receptors are intracellular in D1R co-expressing dendrites.
• Identical results were found for the α1b-adrenergic subtype.

Functional interactions between dopaminergic and noradrenergic systems occur in many brain areas, including the prefrontal cortex (PFC). Biochemical, electrophysiological and behavioral data indicate crosstalk between D1 dopamine receptor (D1R) and α1-adrenergic receptor (α1AR) signaling in the PFC. However, it is unknown whether these interactions occur within the same neurons, or between neurons expressing either receptor. In this study, we used electron microscopy immunocytochemistry to demonstrate that D1Rs and α1ARs co-localize in rat PFC neuronal elements, most prominently in dendrites (60–70%), but also significantly in axon terminals, unmyelinated axons and spines (∼20–30%). Our data also showed that the ratio of plasma membrane-bound to intracellular α1ARs is significantly reduced in D1R-expressing dendrites. Similar results were obtained using either a pan-α1AR or a selective α1bAR antibody to label noradrenergic receptors. Thus, these results demonstrate that D1Rs and α1ARs co-localize in PFC dendrites, thereby suggesting that the catecholaminergic effects on PFC function may be driven, at least in part, by cell-autonomous D1R–α1AR interactions.