From pressure to lost pleasure: the effects of chronic stress on the plasticity of the mesolimbic pathway

Abstract

Depressed patients show anhedonia, a lack of reward-seeking behaviour and motivation. The MCL that controls motivation includes connections from the VTA to the NAc and the mPFC. It is unknown how the MCL is altered in depressed individuals or experimental animals to lead to anhedonia. I intend to find convergent mechanisms in different animal models of stress, which can explain the development of anhedonia in depressed patients. Chronic stress can be modelled through either the CUMS or CSDS paradigm. CUMS-susceptible animals show reduced neuroplasticity and VTA dopaminergic hypoactivity, while CSDS-susceptible animals show increased neuroplasticity and VTA dopaminergic hyperactivity. The resilient animals show similar dopaminergic activity and neuroplasticity as stress-naïve animals.

These contradictory findings can still become a convergent mechanism through the consistent reduction in NAc activity in both models. The NAc of CUMS animals received reduced input from the VTA and the NAc of CSDS animals received excessive BDNF signalling leading to reduced activity of the NAc MSNs.