We use a constellation of techniques and preparations to discover the mechanisms underlying addiction.
Preparations:
At the whole cell level, we study vasopressin and oxytocin-releasing neurons, whose cell bodies and dendritic processes reside in the hypothalamus, and whose terminals reside in the posterior pituitary. This topographic separation offers a unique opportunity to determine differences in drug action within compartments of individual neurons. We also examine neurons from the nucleus accumbens, that play a major role in the reward pathways of the brain, and are likely to participate in addictive behaviors.
At a more reductionist level, we express cloned channel proteins in host cells such as oocytes and human embryonic kidney cells, and study the actions of drugs on these proteins of known composition and homogeneity.
At the most reductionist level, we study cloned proteins that have been removed from transfected cell lines, and incoporate them into artificial planar bilayers. Thus, we have control over both the protein and the lipid environment.
Techniques:
Our techniques include: 1) electrophysiological approaches, including single channel recordings, that allow us to monitor the activity of an individual channel protein, either in biological membrane, or in artificial lipid environments, 2) imaging techniques, such as calcium imaging, that allow us to monitor levels of intracellular calcium, which is an important mediator of drug action and neuronal function, 3) Powerful biophysical techniques, such as atomic force microscopy, that allow us to relate the physical properties of the membrane lipid matrix to the function and pharmacology of individual membrane proteins.