Date Thesis Awarded
Honors Thesis -- Open Access
Bachelors of Science (BS)
Nicotine is extremely addictive, and the negative effects of withdrawal, such as increased anxiety, contribute to relapse. Nicotine produces significant changes in the extended amygdala, the brain regions responsible for regulating anxiety. Light-Enhanced Startle is an established method for assessing anxiety in animal models and is sensitive to drug manipulations. This thesis had two goals, Experiment 1 asked: can LES be used to investigate the anxiety of extended nicotine withdrawal following chronic nicotine administration in rats? We hypothesized that exposing rats to chronic nicotine would result in elevated LES during spontaneous withdrawal as compared to controls, and that this elevation in LES would decrease as withdrawal progressed. Adult Sprague-Dawley rats were given .40 mg/kg nicotine twice daily for 14 days, and were then tested in LES on withdrawal days 1, 3, and 5. Animals showed significantly increased anxiety on withdrawal day 1, and exhibited a pattern of decreasing but elevated LES on withdrawal days 3 and 5 consistent with our predictions. Experiment 2 built on Experiment 1, and asked: what effect will brief nicotine pre-exposure have on the anxiety of withdrawal following later administration? We hypothesized that briefly exposing animals to nicotine, followed by abstinence and then chronic exposure, would potentiate the anxiogenic effects of withdrawal, resulting in even further elevated LES during withdrawal. Adult rats were given 4 days of .40 mg/kg nicotine, followed by 10 days of abstinence, and then chronic nicotine and LES as described above. Surprisingly, animals in Experiment 2 displayed a general decrease in LES, indicating that nicotine pre-exposure has an anxiolytic effect during later withdrawal. These findings demonstrate that nicotine pre-exposure has a significant impact on how the brain responds to later nicotine, and this could be caused by a unique pattern of nAChR desensitization and upregulation resulting from pre-exposure.
Hennings, Augustin C., "Light-Enhanced Startle as an Experimental Model of Withdrawal" (2016). Undergraduate Honors Theses. William & Mary. Paper 947.
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