Fatty Acid Binding Protein (FABP) Inhibitors and Their Neurophysiological Effects on Ventral Tegmental Area (VTA) Dopamine Neurons

Deutsch | Haj-Dahmane
The main goal of this study was to help develop pharmaceutical drugs that may help remedy pain, stress and/or withdrawal from drug abuse.

A novel drug target called the fatty acid binding proteins (FABPs) was discovered by Dr. Dale Deutsch’s group at Stony Brook University. The action of drugs at this target (inhibitors) would raise the levels of naturally occurring “marijuana-like” compounds in the body, endocannabinoids, (eCB) and lead to remedies for pain, stress, and withdrawal from drug abuse. Studies conducted by Dr. Samir Haj-Dahmane at RIA have established that eCBs are released “on demand” by ventral tegmental area (VTA) dopamine neurons, playing a central role in mediating short- and long- term plasticity of glutamate synapses impinging on VTA DA neurons. Together, the researchers investigated whether competitive FABP inhibitors prevent the endocannabinoids from reaching their breakdown enzymes (FAAH and MAGL) and as a result, raise the levels of the endocannabinoids outside the cell at the CB receptors. This research addresses a brain area critically involved in the regulation of stress-related behaviors, such as addiction. The main goal of this study is to develop pharmaceutical drugs that selectively target FABPs, intracellular transporters of eCB, and test their in vitro neurophysiological effects on VTA DA neurons. The working hypothesis is that inhibition of FABPs will elevate eCB levels in the brain, in turn enhancing the neurophysiological effects of eCBs at glutamate synapses of VTA DA neurons. This two-year collaborative project was funded through SUNY REACH (SUNY Research Excellence in Academic Health serving NY at UB, Upstate Medical University, Downstate Medical Center and Stony Brook), 2011-13.