Dopamine D1 Receptor Regulation of Contextual Fear Learning (360G-Wellcome-207206_Z_17_Z)

Post-traumatic stress disorder (PTSD) is characterized by abnormally persistent memories of fear-related stimuli, is inadequately treated with currently available therapies, and is therefore a huge societal and economic burden. Clinical and preclinical evidence implicates key brain regions, such as the hippocampus and amygdala, in the pathophysiology of PTSD and in fear learning and memory processing. During contextual fear conditioning, rodents are trained to associate an environment with receiving aversive electric shock. This entails encoding a representation of the context, which becomes associated with shock. Evidence indicates that dopamine transmission is also crucial for associative learning and we have shown that blocking dopamine D1 receptors in the hippocampus or amygdala impairs contextual fear conditioning (Heath et al., 2015). In this study we will determine the effects of systemic D1 receptor blockade on encoding the contextual representation and the context-shock association in rats by using a two-stage conditioning procedure in which these two dissociable aspects of contextual fear conditioning are encoded separately over two days of training. We will first validate the two-stage conditioning procedure. We will then examine the effects of a D1 receptor antagonist given before the first and/or second day of training, before testing memory drug-free the following day.