Comparison of opioid receptor distributions in the rat central nervous system

Abstract

The opioid receptors, μ, δ and κ, conduct the major pharmacological effects of opioid drugs, and exhibit intriguing functional relationships and interactions in the CNS. Previously established hypotheses regarding the mechanisms underlying these phenomena specify theoretical patterns of relative cellular localisation for the different receptor types. In this study, we have used double-label immunohistochemistry to compare the cellular distributions of δ and κ receptors with those of μ receptors in the rat CNS. Regions of established significance in opioid addiction were examined. Extensive μ/δ co-localisation was observed in neuron-like cells in several regions. μ and κ receptors were also often co-localised in neuron-like cell bodies in several regions. However, intense κ immunoreactivity (ir) also appeared in a separate, morphologically distinct population of cells that did not express μ receptors. These small, ovoid cells were often closely apposed against the larger, μ-ir cell bodies. Such cellular appositions were seen in several regions, but were particularly common in the medial thalamus, the periaqueductal grey and brainstem regions. These findings support proposals that functional similarities, synergy and cooperativity between μ and δ receptors arise from widespread co-expression by cells and intracellular molecular interactions. Although co-expression of μ and κ receptors was also detected, the appearance of a separate population of κ-expressing cells supports proposals that the contrasting and functionally antagonistic properties of μ and κ receptors are due to expression in physiologically distinct cell types. Greater understanding of opioid receptor interaction mechanisms may provide possibilities for therapeutic intervention in opioid addiction and other conditions.