Focal and Drug-Specific Changes in Cerebral Blood Flow in Response to Dose-Controlled Infusion of Alcohol and Morphine in Healthy Young Men

Introduction: One of the primary questions in central nervous system drug development is to identify brain regions with preferential affinity for drug action. Traditionally, information about site-specificity of drug action is drawn from animal (mostly rodent) models. Translational studies expand these findings to human drug research with costly clinical trials based on a-priori assumptions about the site of action and behavioral outcomes of drug actions. Functional neuroimaging methods such as PET and fMRI have been recently used in CNS drug research. However, limitations to repeat PET in the same subject and task-dependency of most of fMRI studies limit the scope of research to hypothesis-based experiments. These limitations potentially obscure important information outside of the a priori hypotheses. If techniques such as continuous arterial spin labeling (CASL) are sensitive enough to reveal site-specific changes in brain perfusion after pharmacological manipulations, then they might offer a repeatable (like fMRI) and quantifiable (like PET) measure of local neural response to different drugs. Previously, we illustrated drug-specific changes in the connectivity of cerebellar, sensory motor and paralimbic brain areas, as observed from examining the topographically correlated changes in restingstate BOLD fluctuations (abstract submitted to this conference). In this parallel study, we have used pseudo CASL (p-CASL) in a similar within-subject placebo-controlled repeated measures study to investigate effects of dose-controlled intravenous infusion of alcohol and morphine on local and global CBF changes.