Autoradiographic localization of kappa opiate receptors to deep layers of the cerebral cortex may explain unique sedative and analgesic effects

Abstract The pharmacologically defined kappa drug 3 H-ethylketazocine ( 3 H-EKC) and 3 H-bremazocine bind to unique sites, but also to mu and delta receptors. By displacing mu and delta interactions with morphine and D-Ala 2 , D-Leu 5 -enkephalin (DADL) respectively we have visualized selective receptors for 3 H-EKC and 3 H-bremazocine. These two kappa ligands are localized to sites different from mu and delta receptors labeled with 3 H-dihydromorphine ( 3 H-DHM) and 3 H-DADL. The highest density and most selective localization of putative kappa receptors occurs in layers V and VI of the cerebral cortex. Cells in these layers project to the thalamus, regulating sensory input to the cortex. These deep cortical kappa receptors may account for the unique sedative and analgesic actions of kappa opiates.