Research in our lab is focused on unraveling the synaptic mechanisms responsible for the complex behavioral and cognitive effects of ethanol. Many projects employ whole-cell patch-clamp electrophysiological methods in rat and mouse brain slice preparations. These powerful electrophysiological techniques allow us to study the physiological and pharmacological properties of excitatory and inhibitory synapses in brain regions that are thought to play an integral role in ethanol addiction. We also employ several rodent self-administration models that provide insight into appetitive and consummatory elements of ethanol drinking behavior.
ONGOING PROJECTS: Behavioral and Synaptic Correlates of Ethanol Drinking: There are a number of projects in progress under this heading. We are currently characterizing a model of voluntary ethanol self-administration in which rats can be trained to drink pharmacologically relevant amounts of ethanol on a daily basis. In one set of experiments, we are using this model to look for behavioral predictors of ethanol seeking and drinking (e.g. initial sensitivity to ethanol, basal anxiety- and impulsivity-like behaviors). In another series of studies we are using whole-cell patch-clamp electrophysiological methods to examine the relationship between ethanol drinking behavior and the acute effects of ethanol on GABAergic synapses in brain regions that are thought to play an important role in mediating ethanol’s reinforcing effects (e.g. hippocampus, nucleus accumbens, amygdala). | 
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Ethanol and Presynaptic GABAB receptors: Ethanol is known to act, in part, by enhancing inhibitory GABAergic synaptic transmission in the central nervous system. This effect results from effects as both pre- and postsynaptic loci. In this project, we are investigating a novel regulatory mechanism involving presynaptic GABAB receptors that serves to limit ethanol’s overall facilitatory effects on GABAergic synapses in several brain regions. Ethanol Mechanisms in GABAA Receptor Gene Targeted Mice: This project is a collaboration with Dr. Gregg Homanics at the University of Pittsburgh. His laboratory has engineered mice with point mutations in specific GABAA receptor subunits. These mutations render GABAA receptors expressing these subunits insensitive to the postsynaptic effects of ethanol without dramatically altering the physiological properties of these receptors. We are using these mice to unravel the relative contribution of pre- and postsynaptic mechanisms to ethanol’s overall potentiating effects on GABAergic synaptic inhibition. | 
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Ethanol, Noradrenaline, and GABAergic Synapses in the Basolateral Amygdala: GABAergic synapses in the basolateral amygdala are known to play an important role in regulating anxiety-like behavior and ethanol potentiation of GABAergic synapses in this nucleus likely contributes to the anxiolytic profile of this drug. In this project, we are characterizing the acute effects of ethanol on GABAergic synapses in this brain region. |