Distribution of the nociceptin and nocistatin precursor transcript in the mouse central nervous system

The distribution of prepronociceptin messenger RNA, the recently identified endogenous ligand of the ORL1 receptor (opioid receptor-like-1), has been studied in the adult mouse central nervous system using in situ hybridizati on. Prepronociceptin is a new peptide precursor that generates, upon matura tion, at least three bioactive peptides: nociceptin, noc2 and the recently described nocistatin. Considering both the density of labeled neurons per r egion and their intensity of labeling, the distribution of prepronociceptin messenger RNA-containing neurons can be summarized as follows: the highest level of prepronociceptin messenger RNA expression was detected in the sep tohippocampal nucleus, bed nucleus of the stria terminalis, central amygdal oid nucleus, and in selective thalamic nuclei such as the parafascicular, r eticular, ventral lateral geniculate and zona incerta. High to moderate lev els of prepronociceptin messenger RNA expression were detected in the later al, ventral and medial septum, and were evident in brainstem structures imp licated in descending antinociceptive pathways (e.g., the gigantocellular n ucleus, raphe magnus nucleus, periaqueductal gray matter), and also observe d in association with auditory relay nuclei such as the inferior colliculi, lateral lemniscus nucleus, medioventral preolivary nucleus and lateral sup erior nucleus. A moderate level of prepronociceptin messenger RNA expressio n was observed in the medial preoptic nucleus, ventromedial preoptic nucleu s, periventricular nucleus, pedonculopontine tegmental nucleus, solitary tr act nucleus and spinal trigeminal nucleus. A weak level of prepronociceptin messenger RNA expression was present in some areas, such as the cerebral c ortex, endopiriform cortex, hippocampal formation, medial amygdaloid nucleu s, anterior hypothalamic area, medial mammillary hypothalamic nuclei, retro rubral field and substantia nigra pars compacta. No labeled cells could be found in the caudate-putamen, nucleus accumbens and ventral tegmental area. The present data confirm that nociceptin is expressed in a broad array of r egions of the central nervous system. In good correlation with the presentl y known physiological actions of nociceptin, they include, amongst others, brain areas conveying/integrating pain and auditory sensory afferences. (C) 1999 IBRO. Published by Elsevier Science Ltd.