Colocalization of μ-Opioid Receptors and Activated G-Proteins in Rat Cingulate Cortex

Abstract

Anterior cingulate cortex (ACC) has a role in pain processing, however, little is known about opioid system organization and actions. This rodent study defines opioid architecture in the perigenual and midcingulate divisions of ACC, relates μ-opioid receptor binding and G-protein activation, and localizes such binding to afferent axons with knife-cut lesions and specifically to noradrenergic terminals with immunotoxin lesions (anti-dopamine β-hydroxylase-saporin; anti-DBH-saporin). [³H]Tyr-d-AlaGly-MePhe-Gly-ol (DAMGO) binding was highest in perigenual areas 32 and 24 with a peak in layer I. Midcingulate area 24′ and posterior cingulate area 29 had overall lower binding in each layer. In contrast, DAMGO-stimulated [³⁵S]guanosine-5′-O-(γ-thio)-triphosphate (GTPγS) binding in area 24′ was similar to that in area 24, whereas area 29 had low and homogeneous binding. Undercut lesions reduced [³H]DAMGO binding in all layers with the greatest loss in layer I (−65%), whereas DAMGO-stimulated [³⁵S]GTPγS binding losses occurred in only layers I-III. Anti-DBH-saporin reduced [³H]DAMGO binding in layer I of area 24; DAMGO-stimulated [³⁵S]GTPγS binding was unchanged in areas 24′ and 29. Correlation analysis of receptor and G-protein activation before and after undercut lesions suggested there were a greater number of DAMGO receptor sites for each G-protein on axons, than on somata and proximal dendrites. Finally, perigenual and midcingulate cortices have different opioid architectures due to a higher proportion of μ-opioid receptors expressed by afferent axons in areas 24 and 32.