Dopamine receptors 1 and 2 in extinction of conditioned fear

Abstract

Post-traumatic stress disorders, the most common type of anxiety disorder, affect more than 800,000 Australians it at any given time. It is currently treated using exposure therapy. In the laboratory, it is commonly modelled by Pavlovian fear conditioning and extinction. It is known that the dopaminergic system plays a major role in fear learning and extinction processes, and therefore presents a potential target for treatment of anxiety disorders. Dopamine activity in the brain is modulated by two main receptors: dopamine receptor 1 and 2 (D1R and D2R, respectively). They are distributed in different regions of the brain, including the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA). This present study wished to explore the patterns of activation of those receptors in the mPFC and BLA in order to gain understanding of the neural circuitry underlying fear. Moreover, the role of parvalbumin positive (PV+) interneurons was investigated, to take into account the inhibitory microcircuitry of extinction. Our results highlighted the importance of the PrL in retrieval of conditioned fear and suggested that stimulation of PV+ interneurons might play a role in this process. It also revealed that D2R signalling in the PrL may be involved in contextual and novelty learning. We observed an interesting correlation between neuronal activation of the PrL and IL, suggesting that these two regions may work in synchronisation and may not be completely dissociated. Overall, the present study provides novel data to the current literature and unveils important information on the neural circuitry underlying extinction of conditioned fear.