Colocalization of mu-opioid receptors and activated G-proteins in rat cingulate cortex

Anterior cingulate cortex (ACC) has a role in pain processing, however, lit tle is known about opioid system organization and actions. This rodent stud y defines opiold architecture in the perigenual and midcingulate divisions of ACC, relates mu -opioid receptor binding and G-protein activation, and l ocalizes such binding to afferent axons with knife-cut lesions and specific ally to noradrenergic terminals with immunotoxin lesions (anti-dopamine bet a -hydroxylase-saporin; anti-DBH-saporin). [H-3]Tyr-D-AlaGly-MePhe-Gly-ol ( DAMGO) binding was highest in perigenual areas 32 and 24 with a peak in lay er 1. Midcingulate area 24' and posterior cingulate area 29 had overall low er binding in each layer. In contrast, DAMGO-stimulated [S-35]guanosine-5'- O-(gamma -thio)-triphosphate (GTP gammaS) binding in area 24' was similar t o that in area 24, whereas area 29 had low and homogeneous binding. Undercu t lesions reduced [H-3]DAMGO binding in all layers with the greatest loss i n layer 1 (-65%), whereas DAMGO-stimulated [S-35]GTP gammaS binding losses occurred in only layers I-III. Anti-DBH-saporin reduced [H-3]DAMGO binding in layer I of area 24; DAMGO-stimulatecl [S-35]GTP gammaS binding was uncha nged in areas 24' and 29. Correlation analysis of receptor and G-protein ac tivation before and after undercut lesions suggested there were a greater n umber of DAMGO receptor sites for each G-protein on axons, than on somata a nd proximal dendrites. Finally, perigenual and midcingulate cortices have d ifferent opioid architectures due to a higher proportion of mu -opioid rece ptors expressed by afferent axons in areas 24 and 32.