Imaging Nociceptin Receptor Expression in Cannabis Use and Psychosis using Positron Emission Tomography with the radioligand [11C]NOP-1A

Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide transmitter in the brain that can suppress neurotransmitter release, including dopamine and glutamate. Therefore, dysregulation of nociceptin opioid peptide receptor (NOPr) signaling can result in neurotransmitter imbalance, suggesting its putative role in substance use disorder and psychosis. Furthermore, N/OFQ has been demonstrated to be involved in the brain’s stress response and in cognitive function. This study presents the first investigation of NOPr in these diseases using the highly specific ligand [11C]NOP-1A and positron emission tomography (PET). Study participants with long-term cannabis use and diagnosed as Clinical High Risk (CHR) and First Episode Psychosis (FEP) were included in the present work. The target regions of interest (ROI) include hippocampus, striatum, medial prefrontal cortex and dorsolateral prefrontal cortex. [11C]NOP-1A binding in the clinical groups was not significantly different compared to healthy volunteers. Cannabis users did not differ in [11C]NOP-1A binding from healthy volunteers and there were no significant group by ROI interactions. [11C]NOP-1A binding was not significantly different between FEP and healthy volunteers with no significant group by ROI interaction. [11C]NOP-1A binding was not significantly different between CHR and healthy volunteers with no significant group by ROI interaction. Interestingly, [11C]NOP-1A binding was associated with cognition in healthy volunteers. We report an interaction between group and immediate and delayed memory scores, such that as memory score increases, [11C]NOP-1A binding in the healthy volunteers decreases. This finding is line with preclinical animal studies that demonstrate N/OFQ agonist treatment or NOPr activation inhibits working memory abilities. In addition, [11C]NOP-1A binding is associated with self-reported stress in cannabis users and CHR. We report an interaction between group and chronic stress such that as stress score increases, [11C]NOP-1A binding in the cannabis users and CHR decreases, but increases in HV. This finding is line with studies that have demonstrated that stress mobilizes the nociceptin receptor system. Our results suggest that cannabis users and CHR patients, which are known to have abnormal stress responses, are unable to upregulate NOPr to counteract stress. Therefore, this may suggest NOPr as a novel target for interventions in these populations.

Department dc:contributor.department

Pharmacology

Year dc:date.issued

2021

Author dc:creator

• Lalang, Nittha Kalyana

Advisor dc:contributor.advisor

• Mizrahi, Romina

• Cannabis Use
• Nociceptin
• PET Imaging
• Psychosis

Handle dc:identifier.uri

http://hdl.handle.net/1807/123113

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/123113