In this study, a novel human laboratory model will be evaluated. Preclinical research indicates acute opioid administration evokes an immune response in the periphery and brain. Here, we will translate those preclinical findings to healthy human volunteers and quantify the neuroimmune response to a morphine challenge (Specific Aim). To measure the neuroimmune system, we will use [11C]PBR28 positron emission tomography (PET) imaging to quantify 18kDa translocator protein (TSPO) availability. TSPO is an imaging marker of the neuroimmune system shown to scale with microglia levels. Up to twenty healthy volunteers will complete two 120-minute [11C]PBR28 PET scans. Subjects will complete one scan prior to, and one scan 2-hr after, a single morphine injection (0.07 mg/kg i.m.). Specific Aim: To determine whether an acute morphine injection increases TSPO availability in healthy volunteers. Hypothesis: Relative to baseline, morphine will significantly increase whole-brain TSPO availability, consistent with a neuroimmune response.
Name: Intramuscular MorphineDescription: Subjects will receive an intramuscular morphine injection (0.07mg/kg) in the non-dominant deltoid muscle. Metoclopramide (10mg; oral) will be administered PRN to reduce nausea.Type: Drug
Acute morphine challenge
Description: The percentage change in 18kDa translocator protein (TSPO) availability from pre-Morphine to post-Morphine measured via PET [11C]PBR28 scansMeasure: Morphine-induced Change in TSPO availability Time: One 120-minute PET [11C]PBR28 scan before and the other ~2 hours after morphine challenge
Description: The percentage change in Cogstate memory performanceMeasure: Morphine-induced Change in Memory Proficiency Time: The Cogstate Battery will be administered twice: once before and once ~1 hours after the morphine challenge
Single Group Assignment
There is one SNP
8. 'Low affinity binding' individuals based on rs6971 polymorphism (<10% of the population).