Organization of endogenous opioids in the rostral agranular insular cortex of the rat

The rostral agranular insular cortex (RAIC) of rats has opioid receptors and has been implicated in the analgesic and reinforcing effects of opiates. To help in understanding the function of endogenous opioids in this structure, we sought to identify and describe the opioid peptides intrinsic to the RAIC by using immunohistochemical methods. Immunolabeling for proopiomelanocortin (POMC), the precursor to beta‐endorphin, and endomorphin 1 and 2 on sectioned rat forebrain revealed limited labeling consisting of individual varicose fibers. Immunolabeling for prodynorphin and enkephalin revealed numerous immunopositive cell bodies and fibers with distribution and morphology unique to each. Prodynorphin‐immunopositive cell bodies consisted of two types: large, lightly labeled, pyramidal‐shaped cell bodies in lamina V and more intensely labeled, small, ovoid cell bodies scattered in other lamina. Axonal fibers immunolabeled for prodynorphin varied in size and were found in all lamina. Immunolabeling for the inhibitory neurotransmitter γ‐aminobutyric acid (GABA) was rarely found in dynorphin‐containing cell bodies (6%, 10/167) but was visible within a subpopulation of axons. Enkephalin immunolabeling was detected within a single morphological subpopulation of nonpyramidal neurons located predominantly in lamina II/III, 30% (33/109) of which were also GABA immunopositive. Axons immunolabeled for enkephalin were also abundant in lamina II/III. These results suggest that dynorphin and enkephalin peptides are the predominant endogenous opioids in the RAIC and their distinct distributions suggest divergent functional roles. The localization of prodynorphin immunoreactivity to pyramidal cells suggests the possibility that this neuropeptide may be used in RAIC projection neurons, whereas enkephalin distribution was more characteristic of a role in local networks. J. Comp. Neurol. 500:530–541, 2007. © 2006 Wiley‐Liss, Inc.