Expression of mu, kappa, and delta opioid receptor messenger RNA in the human CNS: A P-33 in situ hybridization study

The existence of at least three opioid receptor types, referred to as mu, k appa, and delta, is well established. Complementary DNAs corresponding to t he pharmacologically defined mu, kappa, and delta opioid receptors have bee n isolated in various species including man. The expression patterns of opi oid receptor transcripts in human brain has not bean established with a cel lular resolution, in part because of the low apparent abundance of opioid r eceptor messenger RNAs in human brain. To visualize opioid receptor messeng er RNAs we developed a sensitive in situ hybridization histochemistry metho d using P-33-labelled RNA probes. In the present study we report the region al and cellular expression of mu, kappa, and delta opioid receptor messenge r RNAs in selected areas of the human brain. Hybridization of the different opioid receptor probes resulted in distinct labelling patterns. For the mu and kappa opioid receptor probes, the most intense regional signals were o bserved in striatum, thalamus, hypothalamus, cerebral cortex, cerebellum an d certain brainstem areas as well as the spinal cord. The most intense sign als for the delta opioid receptor probe were found in cerebral cortex. Expr ession of opioid receptor transcripts was restricted to subpopulations of n eurons within most regions studied demonstrating differences in the cellula r expression patterns of mu, kappa, and delta opioid receptor messenger RNA s in numerous brain regions. The messenger RNA distribution patterns for ea ch opioid receptor corresponded in general to the distribution of opioid re ceptor binding sites as visualized by receptor autoradiography. However, so me mismatches, for instance between mu opioid receptor receptor binding and mu opioid receptor messenger RNA expression in the anterior striatum, were observed. A comparison of the distribution patterns of opioid receptor mes senger RNAs in the human brain and that reported for the rat suggests a hom ologous expression pattern in many regions. However, in the human brain, ka ppa opioid receptor messenger RNA expression was more widely distributed th an in rodents. The differential and region specific expression of opioid receptors may hel p to identify targets for receptor specific compounds in neuronal circuits involved in a variety of physiological functions including pain perception, neuroendocrine regulation, motor control and reward. (C) 1998 IBRO. Publis hed by Elsevier Science Ltd.