Activation of µ- and ð-opioid receptors enhances dopamine D1-like receptor signalling in mouse medial prefrontal cortex.

In the present study we examined the interaction between opioid and dopamine (DA) D1 - like receptors in the regulation of adenylyl cyclase activity in membranes of microdissected mouse medial prefrontal cortex. We found that the µ-opiooid receptor agonist DAMGO and the ð-opioid receptor agonist DPDPE caused a concentration-dependent potentiation of cyclic AMP formation elicited by either DA or the selective DA D1 -like receptor agonist (+-)-chloro APB. Conversely, the k-opioid receptor agonist (-)U50,488 failed to affect the DA response. The facilitatory effects elicited by DAMGO and DPDPE were mimicked by the naturally occurring opioid agonist leu-enkephalin and completely blocked by the selective µ- and ð-opioid receptor antagonists CTAP and naltrindole, respectively. As prefrontal DA is involved in cognitive and emotional functions, the facilitatory effects on DA D1 –like receptor signaling may represent a novel molecular mechanism contributing to the opioid effects on mood and motivation.