Projects per year
Abstract
Background and Purpose
Predicting the risk of drug-induced adverse psychiatric effects is important but currently not possible in non-human species. This study has investigated whether the affective bias test (ABT) could provide a preclinical method with translational and predictive validity.
Experimental Approach
The ABT is a bowl-digging task which quantifies biases associated with learning and memory. Rats encounter independent learning experiences, on separate days, under either acute manipulations (e.g. pro-depressant vs control) or different absolute reward values (e.g. high vs low). A bias is observed during a preference test when animal’s choices reflect their prior experience. This study investigated the effects of putative pro-depressant drug treatments following acute or chronic administration on the formation of an affective bias or reward-induced positive bias respectively.
Key Results
The immunomodulators lipopolysaccharide (10ug/kg), corticosterone (10, 30mg/kg) and IFN-α (100U/kg) induced a negative affective bias following acute treatment. Tetrabenazine (1mg/kg) also induced a negative bias but no effects were observed with varenicline, carbamazepine or montelukast. Chronic treatment with IFN-α (100U/kg) and retinoic acid (10mg/kg) impaired the formation of a reward-induced positive bias but did not alter sucrose preference test (SPT).
Conclusion and Implications
The ABT has the potential to provide a novel approach to predict pro-depressant risk in a non-human species. Negative biases induced by acute treatment in the standard version of the task may also predict longer term effects on reward processing as shown by the deficit in reward-induced positive bias following chronic treatment, an effect distinct from anhedonia in the SPT.
Predicting the risk of drug-induced adverse psychiatric effects is important but currently not possible in non-human species. This study has investigated whether the affective bias test (ABT) could provide a preclinical method with translational and predictive validity.
Experimental Approach
The ABT is a bowl-digging task which quantifies biases associated with learning and memory. Rats encounter independent learning experiences, on separate days, under either acute manipulations (e.g. pro-depressant vs control) or different absolute reward values (e.g. high vs low). A bias is observed during a preference test when animal’s choices reflect their prior experience. This study investigated the effects of putative pro-depressant drug treatments following acute or chronic administration on the formation of an affective bias or reward-induced positive bias respectively.
Key Results
The immunomodulators lipopolysaccharide (10ug/kg), corticosterone (10, 30mg/kg) and IFN-α (100U/kg) induced a negative affective bias following acute treatment. Tetrabenazine (1mg/kg) also induced a negative bias but no effects were observed with varenicline, carbamazepine or montelukast. Chronic treatment with IFN-α (100U/kg) and retinoic acid (10mg/kg) impaired the formation of a reward-induced positive bias but did not alter sucrose preference test (SPT).
Conclusion and Implications
The ABT has the potential to provide a novel approach to predict pro-depressant risk in a non-human species. Negative biases induced by acute treatment in the standard version of the task may also predict longer term effects on reward processing as shown by the deficit in reward-induced positive bias following chronic treatment, an effect distinct from anhedonia in the SPT.
Original language | English |
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Pages (from-to) | 3200-3210 |
Number of pages | 11 |
Journal | British Journal of Pharmacology |
Volume | 174 |
Issue number | 19 |
Early online date | 30 Aug 2017 |
DOIs | |
Publication status | Published - 1 Oct 2017 |
Bibliographical note
01-Aug-17Fingerprint
Dive into the research topics of 'Using the affective bias test to predict drug-induced negative affect: implications for drug safety'. Together they form a unique fingerprint.Projects
- 2 Finished
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The neurobiology of cognitive affective biases in depression and their role in antidepressant therapy
Robinson, E. S. J. (Principal Investigator)
2/06/14 → 1/09/17
Project: Research
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Investigating the role of neuropsychological processes in stress induced negative affective states and associated behaviour
Robinson, E. S. J. (Principal Investigator)
1/02/14 → 1/02/16
Project: Research
Profiles
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Professor Emma S J Robinson
- School of Physiology, Pharmacology & Neuroscience - Professor of Psychopharmacology
- Bristol Neuroscience
Person: Academic , Member