KAPPA(1) RECEPTOR MESSENGER-RNA DISTRIBUTION IN THE RAT CNS - COMPARISON TO KAPPA-RECEPTOR-BINDING AND PRODYNORPHIN MESSENGER-RNA

Three opioid receptor types have been identified in the CNS and periphery that are referred to as mu, delta, and kappa. The present study examines the mRNA distribution of the kappa(1) receptor in the rat brain and compares it to the distribution of kappa receptor-binding sites and prodynorphin mRNA using a combination of in situ hybridization and receptor autoradiographic techniques. kappa(1) receptor mRNA was localized with a cRNA probe generated with a BamHI-HindIII cDNA fragment of the rat kappa(1) receptor and corresponds to the last 45 bp of the protein coding region and 728 nucleotides of the 3' untranslated region. Prodynorphin mRNA was localized with a cRNA probe corresponding to a 733-bp BamHI-HincII fragment of prodynorphin. kappa receptor-binding sites were labeled in one of two ways: [H-3]U69,593 or [3H]bremazocine in the presence of a 300-fold excess of DAMGO and DPDPE. A high degree of correspondence between the kappa(1) receptor mRNA and kappa receptor binding was observed in several brain regions, including the endopiriform nucleus, claustrum, nucleus accumbens, olfactory tubercle, bed nucleus of the stria terminalis, medial preoptic area, paraventricular, supraoptic, suprachiasmatic, dorsomedial and ventromedial hypothalamic nuclei, basolateral, medial and cortical amygdaloid nuclei, midline thalamic nuclei, periaqueductal grey, parabrachial nucleus, locus coeruleus, and the nucleus of the solitary tract. Differences in the localization of kappa(1) receptor mRNA and binding and the relationship between the distribution of kappa(1) receptor and prodynorphin mRNAs are discussed. (C) 1994 Academic Press, Inc.