RT Journal Article
SR Electronic
T1 An investigation into serotonergic and environmental interventions against depression in a simulated delayed reward paradigm
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 580456
DO 10.1101/580456
A1 Bernd Porr
A1 Alex Trew
A1 Alice Miller
YR 2019
UL http://biorxiv.org/content/early/2019/04/04/580456.abstract
AB The disruption of the serotonergic (5HT) system has been implicated in causing major depression and the standard view is that a lack of serotonin is to blame for the resulting symptoms. Consequently, pharmacological interventions aim to increase serotonin concentration in its target areas or stimulating excitatory 5HT receptors. A standard approach is to use serotonin reuptake inhibitors (SSRIs) which cause a higher accumulation of serotonin. Another approach is to stimulate excitatory serotonin receptors with psychedelic drugs. This paper compares these two approaches by first setting up a system level limbic system model of the relevant brain areas and then modelling a delayed reward paradigm which is known to be disrupted by a lack of 5HT. Central to our model is how serotonin changes the response characteristics of decision making neurons where low levels of 5HT allows small signals to pass through whereas high levels of 5HT create a barrier for smaller signals but amplifying larger ones. We show with both standard behavioural simulations and model checking that SSRIs perform significantly better against interventions with psychedelics. However, psychedelics might work better in other paradigms where a high level of exploration is beneficial to obtain rewards.