Dataset Information

Using the affective bias test to predict drug-induced negative affect: implications for drug safety.

ABSTRACT:

Background and purpose

Predicting the risk of drug-induced adverse psychiatric effects is important but currently not possible in non-human species. We 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 an animal's choices reflect their prior experience. We 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 LPS (10 ?g·kg^-1 ), corticosterone (10 and 30 mg·kg^-1 ) and IFN-? (100 U·kg^-1 ) induced a negative affective bias following acute treatment. Tetrabenazine (1 mg·kg^-1 ) also induced a negative bias, but no effects were observed with varenicline, carbamazepine or montelukast. Chronic treatment with IFN-? (100 U·kg^-1 ) and retinoic acid (10 mg·kg^-1 ) impaired the formation of a reward-induced positive bias but did not alter sucrose preference test (SPT).

Conclusions 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.

Linked articles

This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.

SUBMITTER: Stuart SA

PROVIDER: S-EPMC5595760 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

Using the affective bias test to predict drug-induced negative affect: implications for drug safety.

Stuart S A SA Wood C M CM Robinson E S J ESJ

British journal of pharmacology 20170830 19

<h4>Background and purpose</h4>Predicting the risk of drug-induced adverse psychiatric effects is important but currently not possible in non-human species. We investigated whether the affective bias test (ABT) could provide a preclinical method with translational and predictive validity.<h4>Experimental approach</h4>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 ma ...[more]

PMID: 28782244

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Project description:When an individual attends to certain types of information more than others, the behavior is termed an attention bias. The occurrence of attention biases in humans and animals can depend on their affective states. Based on evidence from the human literature and prior studies in sheep, we hypothesized that an attention bias test could discriminate between pharmacologically-induced positive and negative affective states in sheep. The test measured allocation of attention between a threat and a positive stimulus using key measures of looking time and vigilance. Eighty 7-year-old Merino ewes were allocated to one of four treatment groups; Anxious (m-chlorophenylpiperazine), Calm (diazepam), Happy (morphine) and Control (saline). Drugs were administered 30 min prior to attention bias testing. The test was conducted in a 4 × 4.2 m arena with high opaque walls. An approximately life-size photograph of a sheep was positioned on one wall of the arena (positive stimulus). A small window with a retractable opaque cover was positioned on the opposite wall, behind which a dog was standing quietly (threat). The dog was visible for 3 s after a single sheep entered the arena, then the window was covered and the dog was removed. Sheep then remained in the arena for 3 min while behaviors were recorded. Key behaviors included time looking toward the dog wall or photo wall, duration of vigilance behavior and latency to become non-vigilant. In contrast with our hypothesis, no significant differences were found between treatment groups for duration of vigilance or looking behaviors, although Anxious sheep tended to be more vigilant than Control animals (P < 0.1) and had a longer latency to become non-vigilant (P < 0.001). A total of 24 of 80 animals were vigilant for the entire test duration. This censoring of data may explain why no differences were detected between groups for vigilance duration. Overall, a lack of difference between groups may suggest the test cannot discriminate positive and negative states in sheep. We suggest that the censoring of vigilance duration data, the use of insufficient drug doses, the potential influence of background noise and the age of the sheep may explain a lack of difference between groups. Due to these potential effects, it remains unclear whether the attention bias test can detect positive states in sheep.

Dataset Information

Using the affective bias test to predict drug-induced negative affect: implications for drug safety.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Linked articles

Publications

Using the affective bias test to predict drug-induced negative affect: implications for drug safety.

Similar Datasets

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