Optical Neuroimaging: Studies of the Neuronal and Vascular Effects of Cocaine

Neuroimaging tools have expanded our capabilities for investigating the brain and the effects of drugs such as cocaine on neuronal and vascular function. Here we report on studies that combine different optical imaging methodologies to investigate the effects of cocaine in neurons and those due to its direct effect on vascular function. This multimodality optical approach allows for high-resolution angiographic images of cerebral vessels, quantitative measures of cerebral blood flow, and the assessment of changes in hemoglobin oxygenation and deoxygenation (a marker of tissue metabolism) and intracellular calcium (a measure of neuronal activity). Furthermore, because this approach allows for high spatiotemporal resolutions (e.g., ≤30 μm, ≥10 Hz) and a relatively large field of view (e.g., 3 × 5 mm2), it is possible to assess dynamic changes, which occur rapidly following cocaine exposure. Results have revealed that acute cocaine causes potent vasoconstriction and reduces cerebral blood flow, without affecting neuronal activity, suggesting an uncoupling of blood supply from tissue demands. Furthermore, the vascular effects of cocaine sensitize following chronic drug exposure rendering the cerebral tissue vulnerable to ischemia.