The influence and interaction of the dopaminergic and endocannabinoid system on extinction learning mechanisms


The success or failure of treatments to recover from anxiety related disorders may hinge on individual differences in extinction learning, but these differences remain poorly understood. This project aims to investigate two transmitter systems, as well as their interaction that are both involved in the enhancement of extinction processes: Dopamine (DA) and endogenous Cannabinoids (eCB). We observed previously that the consolidation of extinction learning can be enhanced through administration of the dopaminergic precursor L-DOPA in mice and humans, evident through reduced fear responses and accompanied by activity of the ventromedial PFC (vmPFC) (Haaker et al., 2013, 2015). The first part of this project employs high-resolution fMRI to investigate the impact of a pharmacological challenge on the dopaminergic challenge during extinction learning.The second part of the project focuses on individual differences within the endogenous cannabinoid (eCB) system, and how this system interacts with dopaminergic transmission in the processes of extinction learning. In general, the current project is linked with research projects in animal models (e.g. A04), allowing more fine-grained examinations of underlying molecular mechanisms, as well as it bridges towards investigation in large population of healthy participants (e.g. B01 and B07) and patients (e.g. C02 and C08), where the results can be tested for their general and clinical validity.