Comparing affective bias modification by first- and second-generation antidepressants in male rats using a translational behavioural task

Negative affective biases influence cognitive and emotional behaviours and have been observed in patients with major depressive disorder. The neuropsychological hypothesis of antidepressant efficacy suggests direct modulation of affective biases may contribute to efficacy. Studies have shown conventional antidepressants can positively bias emotional processing following acute administration in humans. This study employs a rat model developed to study affective biases based on associative learning and memory, and used this assay to compare selected first versus second generation antidepressants. Dose-response experiments using the tricyclic antidepressant, amitriptyline (0.3-3.0 mg/kg), monoamine oxidase inhibitor, moclobemide (3.0-10.0 mg/kg) and serotonin specific re-uptake inhibitor, 38 sertraline (1.0-10.0 mg/kg) were performed. Specific protocols permitted quantification of affective biases associated with new learning or the acute and sustained modulation of past experiences. All treatments positively biased new learning but exhibited differences in terms of their ability to modulate negatively biased memories. Amitriptyline and sertraline attenuated negatively biases memories when administered 1 hour or 24 hours before testing. Moclobemide 43 had no effects on past experiences. No treatments had effects in the control reward learning assay. Although generally considered to have similar efficacy and time course of effects, the pharmacological profiles of these antidepressants differ. Previous work has shown that variations in affective bias modification are linked to both the time course of clinical effects and their interaction with experience-dependent plasticity. Integrating understanding of these neuropsychological differences within clinical practice has the potential to improve clinical outcomes for patients.