Brian Hoyt and Dr. Scott Steffensen, Psychology Department
Overview of Project
My research project studied the effects of chronic alcohol intoxication on the brain’s pleasure center (the mesocorticolimbic system). I worked with JungJae Park (M.S. in neuroscience) and three other undergraduate students. Because rats dislike the taste of alcohol, we injected the alcohol directly into their abdominal cavity. This was done under isoflourane anesthesia to avoid any discomfort for the animals. We injected three experimental rats an intoxicating dose of alcohol twice daily for three weeks. Three other rats were used as control subjects (received saline injections twice daily).
During the injection period, we noticed that the rats receiving saline injections were completely normal while those receiving alcohol injections were becoming increasingly sickly. They were lethargic, had malodorous diarrhea, and their abdominal cavities had abnormal lumps upon palpation. Unfortunately, one of the alcohol subjects died prematurely. I performed a post-mortem examination, and discovered that his colon had ruptured, causing his death. This was likely the result of the high alcohol dose.
Following the three-week period of injections, we used fast-scan cyclic voltammetry (FSCV), a novel technique for measuring dopamine levels in live animals. The rats were placed on a stereotaxic table and the experiment was performed under isoflourane anesthesia. First, we drilled two small holes in the skull to allow passage for the electrodes. A stimulating electrode, which delivers an electrical pulse, was positioned in the ventral tegmental area (VTA) of the rat. The VTA connects with and releases dopamine into the nucleus accumbens (NAcc), so we placed a recording electrode in the NAcc to measure the resultant dopamine levels following VTA stimulation.
Results and Conclusions
The experiment went as planned (aside from the premature death of one of our rats). Preliminary analysis of the FSCV data showed that dopamine levels were slightly lower in the alcohol subjects. This indicates that chronic alcohol intoxication may create dependence by hijacking the brain’s pleasure center. When dopamine is released in the NAcc, it causes feelings of pleasure and euphoria (Wise, 2004). Alcohol intoxication transiently excites the VTA, causing an increase of dopamine release in the NAcc. In chronic alcohol intoxication, the brain compensates by inhibiting the projections of the VTA on the NAcc. This causes the depressed dopamine levels seen in our experiment, and this change is likely responsible for the malaise which accompanies withdrawal.
Based on my findings, we will likely expand the study to include more subjects. We are currently exploring chronic alcohol intake in mice (mice have less of an aversion to the taste of alcohol, and will voluntarily become dependent). Because the frequent injections were traumatic for the rats, we are looking into an intoxication chamber. This device would enable us to produce intoxication without the trauma and risk of infection that accompany frequent injections. Our additional studies will enable us to determine if the effect of chronic alcohol intake on the dopamine reward pathway is significant. Our findings will be addressed in JungJae Park’s master’s thesis, and will hopefully be included in a publication or poster produced by Dr. Steffensen.
My participation in mentored research was one of the most significant educational experiences I had at BYU. I enjoyed planning the project, working through difficulties, and seeing it through to completion. Through my experience I gained a more thoughtful, critical, and mature mind. I am grateful to Dr. Scott Steffensen and the Office of Research and Creative Activities for facilitating this valuable, life-changing experience.