Kyle Ellefsen and Dr. Scott Steffensen, Psychology

The nucleus accumbens is a midbrain structure which is thought to influence pleasure and reward. The physiology of this area is also thought to be altered in a state of addiction, including alcoholism. The nucleus accumbens receives most of its dopaminergic input from another midbrain structure, the ventral tegmental area (VTA). The purpose of my research was to characterize the effects of acute ethanol administration on the firing rate of those VTA dopamine neurons by analyzing the change in the electrophysiological properties of inhibitory GABA neurons in the VTA, which are thought to directly regulate VTA dopamine firing rate.

Using the whole cell patch clamp method to record electrical changes in post-synaptic dopamine neurons, I acutely administered ethanol in an artificial cerebrospinal fluid bath which bathed a rat brain slice containing VTA dopamine and GABA neurons and by measuring inhibitory post synaptic currents (IPSCs) in the postsynaptic dopamine neurons, I inferred presynaptic GABAergic activity. I found that IPSCs in VTA dopamine neurons increased dramatically when ethanol was added, indicating an increase in presynaptic GABA activity. This is contradictory to my hypothesis that acute ethanol decreases GABA activity, causing an increase in dopamine, leading to pleasure and reward in the nucleus accumbens.

Studies in my lab and elsewhere show an increase in VTA dopamine firing rate in response to pleasurable stimuli like cocaine or ethanol administration. More research is needed to reconcile the established increase in dopamine firing with my findings, which indicate that the inhibitory GABA transmitter increases. Perhaps excitatory glutamatergic or cholinergic inputs onto VTA dopamine neurons also increase. Other studies have indicated that there are networks of inhibitory GABA networks in the VTA which synapse onto each other and onto dopamine neurons. This complex network, as well as its inputs and outputs, remain poorly characterized and could possibly account for this anomaly. Further understanding of this network will be required before a full understanding of alcohol’s effects on the brain will be illuminated.