Distribution of ORL-1 receptor binding and receptor-activated G-proteins in rat forebrain and their experimental localization in anterior cingulate cortex

Abstract

Opioid receptor-like (ORL-1) receptors and ORL-1-activated G-proteins are found in high levels in the forebrain, particularly cingulate cortex, an area involved in processing of nociceptive stimuli. [3H]nociceptin/orphanin FQ (N/OFQ) and N/OFQ-stimulated [35S]GTPγS autoradiography in rat brain were used to localize ORL-1 receptors and activated G-proteins, respectively. N/OFQ binding and activated G-proteins were highest in anterior cingulate, agranular insula, piriform, perirhinal and entorhinal cortices; midline and intralaminar thalamic nuclei; and subnuclei of the amygdala and hippocampus. In anterior cingulate area 24, [3H]N/OFQ and N/OFQ-stimulated [35S]GTPγS binding were highest in layers V and VI. The cellular localization of ORL-1 receptors and activated G-proteins in area 24 was examined using two strategies: ibotenic acid injection into the cortex or undercut lesions to remove afferent axons, followed by autoradiography. Ibotenic acid lesions that destroyed neurons in the anterior cingulate cortex decreased [3H]N/OFQ binding by 75-80% and reduced N/OFQ-stimulated [35S]GTPγS binding to basal levels seen in the absence of agonist. Deafferentation lesions increased [3H]N/OFQ binding by 40-50%, with no significant change in N/OFQ-stimulated [35S]GTPγS binding. These data demonstrate that ORL-1 receptors in layer V of anterior cingulate cortex are located on somatodendritic elements and that deafferentation increases ORL-1 receptor binding. © 2003 Elsevier Science Ltd. All rights reserved.