Investigating the Neuropsychological Effects of Psychedelics and Their Effect on Emotional Circuits in the Rat Brain

Negative affective biases (the process whereby cognition is modified by emotional state) represent a unique and potentially valuable ‘behavioural biomarker’ for studying emotional symptoms in psychiatric disorders. Unlike traditional questionnaire-based methods which are commonly used to diagnose mental health disorders and assess treatment efficacy, affective biases are quantified using objective behavioural tasks which provide a basis for the development of translational methods for non-human animals. In this talk I will discuss our approach to developing and validating affective bias tests for rodents based on associated reward learning and memory. Using pharmacological and psychosocial manipulations of affective state we have been able to establish the translational validity of this approach and, using targeted brain manipulations and disease models we have also shown that these tasks involve similar underlying mechanisms and vulnerability to stress-induced depression-like phenotypes. Using our affective bias test in rats we have been able to show how conventional versus rapid-acting antidepressants interact with affective biases and that the specific type of modulation they achieve may be related to their time course of clinical effects. We have expanded our studies with both ketamine and the serotonergic psychedelics and this presentation will include some of our most recent developments investigating the circuit mechanisms which may underlie their neuropsychological effects and rapid and sustained antidepressant efficacy.