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Rat ventral midbrain dopamine neurons express the orphanin FQ/nociceptin receptor ORL-1

Orphanin FQ/nociceptin, (OFQ/N) the endogenous ligand for the ORL-1 receptor, has been shown previously to modulate extracellular dopamine concentration in the nucleus accumbens following both intracerebroventricular and intra-ventral tegmental area administration. However, it is unclear whether or not this is a result of a direct action of OFQ/N on ORL-1 receptors located on dopamine neurons. We sought evidence for expression of the ORL-1 receptor in dopamine cells located in the ventral tegmental area and substantia nigra of the rat brain using double-label in situ hybridization. Within the ventral tegmental area, 91% of tyrosine hydroxylase-positive cells were also positive for ORL-1 hybridization. Similarly, in the substantia nigra 90% of tyrosine hydroxylase-positive cells in the zona compacta expressed ORL-1 message and 84% of tyrosine hydroxylase-positive cells in the zona reticulata colocalized ORL-1 message. These data provide the anatomical basis for a direct modulatory effect of OFQ/N on mid-brain dopamine neurons.