Characterization of kappa₁-opioid receptor binding in human insular cortex

Mesolimbic dopaminergic neurotransmission is modulated by dynorphin peptides binding to κ-opioid receptors. The interaction between dynorphin and dopamine systems makes the κ-opioid receptor a potential drug discovery target for the development of therapeutic agents for schizophrenia and drug abuse. This study reports the specificity and parameters of [³H]U69593 binding in the insular cortex, a representative corticolimbic area of the human brain. The results demonstrate that the radioligand [³H]U69593 labels a single population of receptors in human insular cortex with an affinity in the low nanomolar range. The pharmacological profile for inhibition of [³H]U69593 binding was determined in this brain region using drugs known to bind to μ, κ and δ opioid receptors. The results show that κ-opioid selective agonists and antagonists inhibit binding of this ligand in human brain with comparable affinities and rank order as previously described for rat and guinea pig brain and the cloned κ₁-opioid receptor subtype.