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 neuronal from those of 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 in 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 cocaine causes potent vascular effects and acutely reduces cerebral blood flow, without effecting neuronal activity, suggesting an uncoupling of blood supply from tissue demands. Furthermore, the vascular effects of cocaine have been found to be sensitized following chronic drug exposure rendering the cerebral tissue vulnerable to ischemia.