Vol. 299, Issue 3, 840-848, December 2001

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

Leslie J. Vogt , Laura J. Sim-Selley, Steven R. Childers, Ronald G. Wiley and Brent A. Vogt

Cingulum NeuroSciences Institute, Syracuse, New York (L.J.V., B.A.V.); Department of Physiology and Pharmacology and Center for Investigative Neuroscience, Wake Forest University School of Medicine, Winston-Salem, North Carolina (L.J.V., S.R.C., B.A.V.); Department of Pharmacology and Toxicology and Institute for Drug and Alcohol Studies, Virginia Commonwealth University Medical College of Virginia, Richmond, Virginia (L.J.S.-S.); and Neurology Service (127), Veterans Administration Medical Center, and Departments of Neurology and Pharmacology, Vanderbilt University, Nashville, Tennessee (R.G.W.)

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 -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-(-thio)-triphosphate (GTPS) 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]GTPS binding losses occurred in only layers I-III. Anti-DBH-saporin reduced [³H]DAMGO binding in layer I of area 24; DAMGO-stimulated [³⁵S]GTPS 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.