Expression of orphanin FQ and the opioid receptor-like (ORL1) receptor in the developing human and rat brain

The orphanin peptide system, although structurally similar to the endogenou s opioid family of peptides and receptors, has been established as a distin ct neurochemical entity. The distribution of the opioid receptor-like (ORL1 ) receptor and its endogenous ligand orphanin FQ (OFQ) in the central nervo us system of the adult rat has been recently reported, and although diffuse ly disseminated throughout the brain, this neuropeptide system is particula rly expressed within stress and pain circuitry. Little is known concerning the normal expression of the orphanin system during gestation, nor how opia te or stress exposure may influence its development. Using in situ hybridiz ation techniques, the present study was undertaken to determine the normal pattern of expression of ORL1 mRNA in the human and rat brain at various de velopmental stages. Rat embryos, postnatal rat brains and postmortem human brains were collected. frozen and cut into 15 [im coronal sections. In situ hybridization was performed using riboprobes generated from cDNA containin g representative human and rat ORL1 and OFQ sequences. Both ORL1 and OFQ mR NA is detected as early as E12 in the cortical plate, basal forebrain, brai nstem and spinal cord. Expression for both ORL1 and OFQ is strongest during the early postnatal period, remaining strong in the spinal cord, brainstem . ventral forebrain, and neocortex into the adult. Human ORL1 and OFQ expre ssion is observed at 16 weeks gestation, remaining relatively unchanged up to 36 weeks. The influence of early orphanin expression on maturation of st ress and pain circuitry in the developing brain remains unknown. (C) 2001 E lsevier Science B.V. All rights reserved.