Thursday, November 21, 2024
11/21/2024
Project Summary The majority of alcohol users in the US consume alcohol at doses and frequencies that are not consistent with alcohol use disorder (AUD). There is growing evidence that low-dose ethanol exposure impacts the brain and behavior but despite this, the behavioral and neurobiological consequences of chronic low-dose alcohol consumption are poorly understood. The decision to seek a reward has a direct relationship with its value. The ability to reassess and update reward value is critical for adaptive value-guided decision making. Deficits in the processes that moderate motivated behavior may contribute to the transition from casual alcohol consumption to AUD. Data from our lab indicate that chronic low-dose ethanol enhances reward motivation in a progressive ratio (PR) task in male, but not female, mice. In contrast, ethanol-exposed female mice are more sensitive to reduced reward value than ethanol-naïve females, whereas ethanol exposure did not increase sensitivity to change in reward value in males. These changes may result from an ethanol-induced dysregulation in the ability to use reward value information to guide behavior, which can be determined experimentally through the use of a value-guided decision making task. One potential neurobiological substrate mediating this effect is the basolateral amygdala (BLA). The BLA is a key neuroanatomical substrate of reward value encoding and participates in updating value information and influencing value-guided decision making. Preliminary data from our lab suggest that chronic low-dose ethanol exposure decreases cFos expression in BLA and its projections to the nucleus accumbens (NAc) following reward seeking. This proposal will test the overarching hypothesis that chronic-low-dose ethanol alters BLA glutamate receptor expression, thus contributing to impairments in detecting and using reward value information to guide behavior. In Aim 1, we will use a value-guided decision- making task to test our hypothesis that chronic low-dose ethanol impairs the ability to update changes in reward value for adaptive behavior. In Aim2, we will investigate the impact of chronic low-dose ethanol exposure on BLA and NAc postsynaptic glutamate receptors and the relationship between these changes and performance on the value-guided decision-making task. Aim 3 will use chemogenetic strategies to test the hypothesis that inhibiting the BLA or BLA → NAc circuit activity will impair the ability to successfully use reward value information during a value-guided decision-making task. The results from these experiments will expand our understanding of the impacts of chronic low-dose ethanol exposure on behavior and neurobiology, which is an area that remains severely understudied in the alcohol use field. Further, this fellowship will enable the applicant to build on her expertise in learning and memory processes which may be dysregulated by alcohol use by integrating a conceptual understanding of low-dose ethanol effects on molecular substrates, specific circuits, and behavior. The abundance of resources and opportunities available in the Barker lab and at Drexel University will ensure that the applicant is prepared and qualified for an independent alcohol research career.
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