COMBINING MOLECULAR GENETIC APPROACHES TO STUDY MOTIVATED BEHAVIORS RELATED TO SUBSTANCE USE DISORDER.

We use a variety of simple to complex rodent behavioral paradigms to quantify behavior relevant to discrete domains of Substance Use Disorder. Our main focus is on domains of drug withdrawal. Opioid withdrawal includes a physical signs, which we measure by video tracking and scoring. Opioid withdrawal also includes negative affective states such as anhedonia, dysphoria, and anxiety. To measure anhedonia (reduction in pleasure/reward sensitivity) we use Intracranial Self-Stimulation (ICSS), which quantifies shifts in reward function in real time. To measure dysphoria and disruptions in associative memory, we use Place Conditioning. To measure anxiety-like behavior we use the Elevated Plus Maze and/or Open Field test. Drug withdrawal is also associated with an increased sensitivity to stress, and we use exposure to the Forced Swim test as one such stressor.

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We use a variety of molecular and anatomical methods to identify neurobiological mechanisms underlying drug withdrawal-induced behaviors. To measure drug- or drug withdrawal-induced changes in gene and protein expression, we use qRT-PCR, protein immunoblotting, and immunohistochemistry. To identify relevant neural circuits, we use a combination of retrograde tracing and pharmacological approaches. 

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To causally link molecular and circuit mechanisms to behavior, we use a combination of behavioral pharmacology and viral vector-mediated modulation of gene/protein expression in brain regions of interest and assess the impact on drug withdrawal-induced behaviors.