Abstract
RationaleReward-related impairments are common in major depressive disorder (MDD) and may contribute to the loss of interest in pleasurable activities. A novel approach to studying reward-related decision-making are effort-based tasks; however, direct comparisons between delayed-onset and rapid-acting antidepressants (ADs) have not yet been carried out.ObjectivesTo investigate the effects of conventional delayed-onset ADs versus rapid-acting ADs, ketamine and scopolamine, on effort-related choice behaviour.MethodsFemale Lister hooded rats were trained in an operant effort for reward task (EfRT) where animals choose between working for a high value-high effort reward and consuming low value-low effort chow. Using a within-subject study design, animals were then tested following acute treatment with different monoaminergic ADs, and the rapid-acting ADs ketamine or scopolamine.ResultsConsistent with previous findings, we found choice behaviour was sensitive to dopaminergic manipulations. We observed that pre-feeding altered choice behaviour and that the use of high or low value reward differentially affected behaviour. Monoamine re-uptake inhibitors and rapid-acting ADs resulted in similar, general patterns of reduced motivation without any evidence for specific effects, and we did not observe any clear differences between these classes of antidepressant.ConclusionsMotivational changes induced by dopaminergic manipulations and pre-feeding differentially affect effort choice behaviour. However, both conventional delayed-onset ADs and ketamine and scopolamine appear to have detrimental effects on motivation in this task at the higher doses tested without any evidence of specificity for effort-related choice behaviour, in contrast to their specificity in tasks which look at more cognitive aspects of reward processing.
Highlights
Major depressive disorder (MDD) is one of the leading causes of disability worldwide, accounting globally for 8.2% of all years lived with disability (Ferrari et al 2013)
Anhedonia is a complex symptom consisting of consummatory and motivational components (Der-Avakian and Markou 2012; Slaney et al 2018); changes in reward-related behaviour in depression may be more complex, and recent human and animal studies suggest that changes in more cognitive aspects of reward processing may be relevant (Thomsen 2015; Slaney et al 2018)
Fluoxetine had no effect on either the bursting activity or the behaviour (Yang et al 2018). These findings suggest that affective biases related to reward learning, memory, and decision-making are differentially modulated by ketamine versus delayed-onset antidepressant drugs (ADs)
Summary
Major depressive disorder (MDD) is one of the leading causes of disability worldwide, accounting globally for 8.2% of all years lived with disability (Ferrari et al 2013). Psychopharmacology (2020) 237:2381–2394 and Statistical Manual of Mental Disorders 5 (DSM5) (American Psychiatric Association 2013). Anhedonia is a complex symptom consisting of consummatory and motivational components (Der-Avakian and Markou 2012; Slaney et al 2018); changes in reward-related behaviour in depression may be more complex, and recent human and animal studies suggest that changes in more cognitive aspects of reward processing may be relevant (Thomsen 2015; Slaney et al 2018). The DSM5 lists the symptom of ‘loss of interest in rewarding activities’ as an important contributor to MDD which may be influenced by anhedonia or by wider deficits in reward-related behaviour (American Psychiatric Association 2013). Ketamine, a rapidacting AD, rapidly and robustly ameliorates anhedonia in patients with treatment-resistant depression and treatmentresistant bipolar depression (Murrough et al 2013; Lally et al 2014)
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