The role of dopamine D1/5 receptors in fear and reward

Extinction learning, which inhibits conditioned stimulus–unconditioned stimulus associations, is influenced by dopamine signaling and has clinical relevance for disorders such as PTSD and addiction. This dissertation examines the role of dopamine D1/5 receptors in fear and reward extinction using pharmacological manipulations, knockout models, and intracranial microinjections. Findings show that methylphenidate and D1/5 receptor agonist SKF 81297 enhance fear extinction and cocaine reward extinction, while D1 receptor knockout alters fear expression without impairing acquisition. Mechanistic studies implicate PKA-coupled D1/5 receptor signaling in extinction enhancement. Results suggest dopamine signaling contributes to extinction processes and may inform therapeutic strategies.