THE DISTRIBUTION OF IMMUNOREACTIVE a-NEO-ENDORPHIN IN THE CENTRAL NERVOUS SYSTEM OF THE RAT

Using a specific radioimmunoassay, we have found that immunoreactive (ir) a-neo-endorphin has a widespread and unique distribution in the rat brain and spinal cord. The highest concentration in brain is in the substantia nigra (1692.1 fmol/mg of protein). Very high concentrations of ir-a-neoedorphin (X00 fmol/mg of protein) are also found in the lateral preoptic nucleus, dentate gyrus, parabrachial nuclei, nucleus accumbens, globus pallidus, median eminence, and anterior hypothalamic nucleus. Relatively high concentrations of ir-a-neo-endorphin (250 to 500 fmol/mg of protein) are present in the bed nucleus of the stria terminalis, paraventicular nucleus, nucleus of the solitary tract, dorsomedial nucleus, central amygdaloid nucleus, periaqueductal gray matter, suprachiasmatic nucleus, periventricular nucleus, hippocampus, prepositus hypoglossal nucleus, arcuate nucleus, ventromedial nucleus, medial preoptic nucleus, zona incerta, dorsal premamillary nucleus, medial forebrain bundle (hypothalamic and preoptic), nucleus of the diagonal band, locus ceruleus, lateral septal nucleus, and nucleus ambiguus. Moderate levels (100 to 250 fmol/mg of protein) are found in the posterior hypothalamic nucleus, ventral premamillary nucleus, dorsal raphe nucleus, motor hypoglossal nucleus, caudate-putamen, periventricular thalamic nucleus, subcommissural organ, sensory trigeminal nucleus, perifornical nucleus, area postrema, supraoptic nucleus, cuneate nucleus, medial amygdaloid nucleus, and organum vasculosum laminae terminalis. Low concentrations of ira-neo-endorphin (-400 fmol/mg of protein) are found in many cortical structures, claustrum, thalamic nuclei, habenular nuclei, lateral geniculate body, red nucleus, superior and inferior colliculi, paramedian reticular nucleus, pontine nuclei, superior olive, vestibular nuclei, motor facial nucleus, gigantocellular reticular nucleus, and subfornical organ. The lowest concentrations in brain (~50 fmol/mg of protein) were measured in the olfactory bulb, and cerebellar cortex and nuclei. The spinal cord (cervical, thoracic, and lumbar segments) has low levels of ir-ol-neo-endorphin. cy-Neo-endorphin is a 10 amino acid opioid peptide cell bodies, fibers, and terminals in the magnocellular originally isolated from porcine hypothalami (Kangawa hypothalamic nuclei, entorhinal cortex, central nucleus et al., 1979). It contains the amino acid sequence of of the amygdala, hippocampal dentate gyrus, periaqueleucine (Leu)-enkephalin at its amino terminus (Kanductal gray matter, parabrachial nuclei, brain stem reticgawa et al., 1981) and has extraordinary potency as an ular formation, nucleus of the spinal tract of trigeminal opiate agonist in the in vitro guinea pig myenteric plexusnerve, nucleus of the solitary tract, cuneate nucleus and longitudinal muscle bioassay (Kangawa et al., 1979,1981; the spinal cord (Weber er al., 1982a). In addition, ir-aOka et al., 1982). It appears to be highly selective K opiate neo-endorphin/dynorphin fibers or terminals were demagonist (Corbett et al., 1982; Oka et al., 1982). a-Neoonstrated in the cerebral cortex, olfactory bulb, nucleus endorphin and the dynorphins are derived from a comaccumbens, caudate-putamen, globus pallidus, hippomon precursor (prodynorphin) which contains three Leucampus, preoptic area, median eminence, substantia nienkephalin sequences (Kakidani et al., 1982). These corgra (reticular part), locus ceruleus, trigeminal sensory respond to neo-endorphin (Kangawa et al., 1981), dynornucleus, motor facial nucleus, nucleus raphe magnus, phin A (dyn A) (Goldstein et al., 1981), and dynorphin certain vestibular and cochlear nuclei, reticular formaB (dyn B) (Kilpatrick et al., 1982), respectively. tion, and dorsal horn of the spinal cord, as well as the Immunohistochemical studies have shown the existneural lobe of the pituitary (Weber et al., 1982a). Imence of immunoreactive (ir) a-neo-endorphin/dynorphin munohistochemical methods allow precise localization of neuropeptides in brain structures but do not permit ’ To whom correspondence should be addressed. quantitation of the neuropeptide. Until now, the distri-