Neuroanatomical localization of κ₁ and κ₂ opioid receptors in rat and guinea pig brain

The neuroanatomical localization of κ opioid receptors in rat and guinea pig brain was determined by quantitative in vitro receptor autoradiography. Our study shows striking differences in k₁ and k₂ receptor distributions both between species and within each species. In the rat brain, κ₁ sites (labeled by [³H]U-69,593) are of low density and confined to a small number of structures. These include the claustrum, endopiriform nucleus, caudate putamen, nucleus accumbens, midline nuclear group of the thalamus, superficial grey layer of the superior colliculus, and central grey. κ₂ sites (labeled by [³H]ethylketocyclazocine or [³H]bremazocine under conditions in which μ, δ, and κ₁ binding was suppressed) are more widely distributed throughout all levels of rat brain. κ₂ sites occur at high density in the caudate putamen, nucleus accumbens, amygdala, thalamus, and interpeduncular nuclei. In guinea pig brain, κ₁ sites predominate and are of high density in layers I and VI of the neocortex, claustrum, endopiriform nucleus, caudate putamen, nucleus accumbens, and molecular layeer of the cerebellum. As in rat brain, κ₂ sites in guinea pig are more uniformly and widely distributed throughtout the brain than are κ₁ sites. The highest density of κ₂ sites is in the dorsal parabrachial nucleus, interpeduncular nuclei, mammillary nuclei, and posterior thalamic nuclei. Results from this study demonstrate important interspecies differences in the distribution of κ₁ and κ₂ opioid receptors. In particular, κ₁ receptors found in high density in layers I and VI of guinea pig neocortex and their virtual absence in the corresponding cortical layers of rat brain might mediate the enhanced analgesic response to κ opioids exhibited by guinea pigs relative to rats. The differences in neuroanatomical localization of κ₁ and κ₂ receptors within each species provide further support for heterogeneity in the κ opioid receptor system.