Elsevier

Neuroscience

Volume 121, Issue 3, 15 October 2003, Pages 629-640
Neuroscience

[3h]-nociceptin ligand-binding and nociceptin opioid receptor mrna expression in the human brain

https://doi.org/10.1016/S0306-4522(03)00484-6Get rights and content

Abstract

Following the cloning of the novel nociceptin opioid receptor (NOP1) and the identification of its endogenous ligand orphanin FQ/nociceptin the distribution and functional role of the NOP1 receptor system have been studied mainly in the rodent CNS. In the present study the regional distribution and splice variant expression of the NOP1 receptor was investigated in the adult human brain using [3H]-nociceptin autoradiography, NOP1 reverse transcriptase PCR and mRNA in situ hybridization.

Ligand binding revealed strong expression of functional NOP1 receptors in the cerebral cortex and moderate signals in hippocampus and cerebellum. Interestingly, the NOP1 receptor specific ligand was also strongly bound in the human striatum. A matching pattern of mRNA expression was observed with high amounts of NOP1 mRNA in the prefrontal and cingulate cortex as well as in the dentate gyrus of the hippocampus. mRNA levels in the Ammon's horn and cerebellar cortex were moderate and low in the striatum. A considerable expression of N-terminal NOP1 splice variant mRNAs was not detectable in the human brain by means of in situ hybridization. This suggests that functional NOP1 receptors in the human brain are encoded by N-terminal full length NOP1 transcripts.

The present data on the anatomical distribution of nociceptin binding sites and NOP1 receptor mRNA contribute to the knowledge about opioid receptor systems in the human brain and may promote the understanding of function and pharmacology of the orphanin FQ/nociceptin receptor system in the human CNS.

Section snippets

Tissue acquisition and slice preparation

Human brain tissues (n=4) were obtained from male patients at medicolegal autopsy. Patients (age: 56–67 years, mean 61 years) had died from heart failure (n=3) or car accident. None of the patients had a history of neurological or psychiatric disease. With a postmortem interval of mean 19.0 h (6–29.5), brain tissues were removed for diagnostic reasons. Representative tissue blocks were prepared and rapidly frozen on dry ice. Sections (20 μm) of brain tissue used in the present study were cut on

Results

In the present study, the differential expression of NOP1 receptors in the human brain (cortex, basal ganglia, hippocampal area and cerebellum) was investigated by utilizing on-section ligand binding corroborated with mRNA detection on parallel sections of the same brain tissues. In general, [3H]-nociceptin ligand binding and NOP1 receptor mRNA expression were widespread and indicative of a considerable high NOP1 receptor expression in these anatomical regions.

[3H]-nociceptin ligand binding was

Discussion

Although the neuroanatomical distribution of the NOP1 receptor has been well characterized in the rodent CNS, to date no data have been presented regarding the expression of this opioid receptor in the adult human brain. The present study closes this gap by describing the patterns of nociceptin ligand binding and NOP1 receptor mRNA expression in neurologically normal adult human postmortem brain. By corroborating binding sites with corresponding sites of transcript expression, this combination

Acknowledgements

This work was supported by SFB 391 of the Deutsche Forschungsgemeinschaft.

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