Potentiation of dopamine D1-like receptor signaling by concomitant activation of δ- and μ-opioid receptors in mouse medial prefrontal cortex.
Opioid receptors located in the ventral tegmental area are known to regulate dopamine (DA) release from mesocortical afferents to medial prefrontal cortex (mPFC) but little is known on whether in this cortical region activation of opioid receptors affect DA receptor signaling. In the present study we show that in mouse mPFC concomitant activation of either δ- or μ-opioid receptors, but not κ-opioid receptors, potentiated DA D1-like receptor-induced stimulation of adenylyl cyclase activity through a G protein βγ subunit-dependent mechanism. In tissue slices of mPFC, the combined addition of the opioid agonist leu-enkephalin and the DA D1-like receptor agonist SKF 81297 produced more than additive increase in the phosphorylation state of AMPA and NMDA receptor subunits GluR1 and NR1, respectively. Moreover, in primary cultures of mouse frontal cortex neurons, DA D1-like receptor-induced Ser133 phosphorylation of the transcription factor cyclic AMP responsive element binding protein was potentiated by concurrent stimulation of opioid receptors. Double immunofluorescence analysis of cultured cortical cells indicated that a large percentage of DA D1 receptor positive cells expressed either δ- or μ-opioid receptor immunoreactivity. These data indicate that in mouse mPFC activation of μ- and δ-opioid receptors enhances DA D1-like receptor signaling likely through converging regulatory inputs on βγ-stimulated adenylyl cyclase isoforms. This previously unrecognized synergistic interaction may selectively affect DA D1 transmission at specific postsynaptic sites where the receptors are co-localized and may play a role in prefrontal DA D1 regulation of opioid addiction.
Section of Neurosciences, Department of Biomedical Sciences University of Cagliari, Cagliari, Italy.
Maria C
MC
Olianas
Simona
S
Dedoni
Pierluigi
P
Onali
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005625:Frontal Lobe / Q000166:cytology; D044387:GTP-Binding Protein beta Subunits / Q000502:physiology; D044388:GTP-Binding Protein gamma Subunits / Q000502:physiology; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D018091:Receptors, AMPA / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*
D000262:Adenylyl Cyclases; D001552:Benzazepines; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004298:Dopamine; D018491:Dopamine Agonists; D004743:Enkephalin, Leucine; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D009419:Nerve Tissue Proteins; D018847:Opioid Peptides; D020033:Protein Isoforms; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C492004:Creb1 protein, mouse; C118981:G-protein Beta gamma; C121673:Gprin1 protein, mouse; C067113:SK&F 81297