Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI

摘要: Background and purpose: Activation of cannabinoid CB1 and/or CB2 receptors mediates analgesic effects across a broad spectrum preclinical pain models. Selective activation may produce analgesia without the undesirable psychotropic side associated with modulation receptors. To address selectivity in vivo, we describe non-invasive, non-ionizing, functional data that distinguish from receptor neural activity using pharmacological MRI (phMRI) awake rats. Experimental approach: Using high field (7 T) scanner, examined quantified non-selective CB1/CB2 (A-834735) selective (AM1241) agonists on rats. Pharmacological specificity was determined (rimonabant) or (AM630) antagonists. Behavioural studies, plasma brain exposures were used as benchmarks for vivo. Key results: The agonist produced dose-related, region-specific structures agrees well published autoradiographic density binding maps. Pretreatment antagonist but not antagonist, abolished these patterns, suggesting an effect mediated by alone. In contrast, no significant changes found relevant doses agonist. Conclusion implications: These results provide first clear evidence quantifying vivo between phMRI. Further, presence remains controversial, our suggest if are expressed, they under normal physiological conditions. British Journal Pharmacology (2008) 153, 367–379; doi:10.1038/sj.bjp.0707506; online 29 October 2007