ULTRASTRUCTURAL-LOCALIZATION OF DELTA-OPIOID RECEPTOR AND MET(5)-ENKEPHALIN IMMUNOREACTIVITY IN RAT INSULAR CORTEX

The insular cortex has been implicated in the reinforcing properties o f opiates as well as in the integration of responses to sensory-motor stimulation. Moreover, the delta-opioid receptor (DOR) and the endogen ous opioid ligand, Met(5)-enkephalin (ENK) are known to be prominently distributed in insular limbic cortex. To examine the anatomical sites for opioid activation of DOR in rat insular cortex, we used immunoper oxidase for detection of an antiserum raised against a peptide sequenc e unique to the DOR alone, and in combination with immunogold-silver l abeling for ENK. Light microscopy showed intense DOR-like immunoreacti vity (DOR-LI) in pyramidal cells and interneurons in deep laminae, and in varicose processes in both superficial and deep layers of the insu lar cortex. Ultrastructural analysis of layers V and VI in insular cor tex showed that the most prominent immunoperoxidase labeling for DOR w as in dendrites. This labeling was associated with asymmetric excitato ry-type junctions postsynaptic to unlabeled terminals. Dendritic DOR-L I was also distributed along selective portions of non-synaptic plasma membranes and subsurface organelles. In dually labeled sections, dend rites containing DOR-LI sometimes received synaptic input from ENK-lab eled terminals or more infrequently colocalized with ENK. Other axon t erminals were exclusively immunolabeled for DOR or more rarely contain ed both DOR and ENK immunoreactivity. Within labeled axon terminals, d istinct segments of the plasma membrane and membranes of immediately a djacent synaptic vesicles showed the largest accumulation of the perox idase reaction product for DOR. These results indicate that in rat ins ular cortex DOR is primarily heteroreceptive, but also serves an autor eceptive function on certain ENK-containing neurons. Our results also provide the first ultrastructural evidence that in rat insular cortex endogenous opioids interact through the DOR (1) to modulate the postsy naptic responses to other excitatory afferents and (2) to presynaptica lly regulate the release of other neurotransmitters. The modulatory ac tions on both EMC-containing and non-ENK-containing neurons may contri bute significantly to the reinforcing properties of exogenous opiates acting on the DOR in limbic cortex.