Intervenants > Angela Roberts

Angela Roberts

U. Cambridge, UK

Application de DREADDS pour étudier la régulation préfrontale des réseaux sous-corticaux impliqués dans la réponse à la récompense et la menace chez le marmoset

Anxiety and anhedonia are two distinct symptoms associated with several psychiatric disorders. Recently we have shown that overactivation in a key dysfunctional region in depression, subcallosal cingulate area 25 (scACC-25), induces both anticipatory and motivational anhedonia as well as heightened responsivity to certain and uncertain threat. Since we have shown that scACC-25 engages a distinct network of structures in appetitive and threatening environments we investigated whether distinct pathways from scACC-25 were involved in these two opposing effects of scACC-25 overactivation.  Utilising Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) we assessed the specific impact of over-activating individual scACC-25 pathways to the nucleus accumbens and amygdala on reward and threat responsivity. Controlling for off target effects by metabolites of the DREADD activator, Clozapine N-oxide, we show that the scACC-25 to accumbens pathway mediates anticipatory anhedonia but not heightened anxiety whilst the scACC-25 to amygdala pathway mediates heightened anxiety but not anticipatory anhedonia. We discuss this in relation to our understanding not only of the aetiology but also the treatment of these two major psychiatric symptoms