Header

UZH-Logo

Maintenance Infos

Establishing operant conflict tests for the translational study of anxiety in mice


Oberrauch, Sara; Sigrist, Hannes; Sautter, Eva; Gerster, Samuel; Bach, Dominik R; Pryce, Christopher R (2019). Establishing operant conflict tests for the translational study of anxiety in mice. Psychopharmacology, 236(8):2527-2541.

Abstract

RATIONALE In conflict-based anxiety tests, rodents decide between actions with simultaneous rewarding and aversive outcomes. In humans, computerised operant conflict tests have identified response choice, latency, and vigour as distinct behavioural components. Animal operant conflict tests for measurement of these components would facilitate translational study.
OBJECTIVES In C57BL/6 mice, two operant conflict tests for measurement of response choice, latency, and vigour were established, and effects of chlordiazepoxide (CDZ) thereon investigated.
METHODS Mice were moderately diet-restricted to increase sucrose reward salience. A 1-lever test required responding under medium-effort reward/threat conditions of variable ratio 2-10 resulting in sucrose at p = 0.7 and footshock at p = 0.3. A 2-lever test mandated a choice between low-effort reward/threat with a fixed-ratio (FR) 2 lever yielding sucrose at p = 0.7 and footshock at p = 0.3 versus high-effort reward/no threat with a FR 20 lever yielding sucrose at p = 1.
RESULTS In the 1-lever test, CDZ (7.5 or 15 mg/kg i.p.) reduced post-trial pause (response latency) following either sucrose or footshock and reduced inter-response interval (increased response vigour) after footshock. In the 2-lever test, mice favoured the FR2 lever and particularly at post-reward trials. CDZ increased choice of FR2 and FR20 responding after footshock, reduced response latency overall, and increased response vigour at the FR2 lever and after footshock specifically.
CONCLUSIONS Mouse operant conflict tests, especially 2-lever choice, allow for the translational study of distinct anxiety components. CDZ influences each component by ameliorating the impact of both previous punishment and potential future punishment.

Abstract

RATIONALE In conflict-based anxiety tests, rodents decide between actions with simultaneous rewarding and aversive outcomes. In humans, computerised operant conflict tests have identified response choice, latency, and vigour as distinct behavioural components. Animal operant conflict tests for measurement of these components would facilitate translational study.
OBJECTIVES In C57BL/6 mice, two operant conflict tests for measurement of response choice, latency, and vigour were established, and effects of chlordiazepoxide (CDZ) thereon investigated.
METHODS Mice were moderately diet-restricted to increase sucrose reward salience. A 1-lever test required responding under medium-effort reward/threat conditions of variable ratio 2-10 resulting in sucrose at p = 0.7 and footshock at p = 0.3. A 2-lever test mandated a choice between low-effort reward/threat with a fixed-ratio (FR) 2 lever yielding sucrose at p = 0.7 and footshock at p = 0.3 versus high-effort reward/no threat with a FR 20 lever yielding sucrose at p = 1.
RESULTS In the 1-lever test, CDZ (7.5 or 15 mg/kg i.p.) reduced post-trial pause (response latency) following either sucrose or footshock and reduced inter-response interval (increased response vigour) after footshock. In the 2-lever test, mice favoured the FR2 lever and particularly at post-reward trials. CDZ increased choice of FR2 and FR20 responding after footshock, reduced response latency overall, and increased response vigour at the FR2 lever and after footshock specifically.
CONCLUSIONS Mouse operant conflict tests, especially 2-lever choice, allow for the translational study of distinct anxiety components. CDZ influences each component by ameliorating the impact of both previous punishment and potential future punishment.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

2 downloads since deposited on 17 Oct 2019
2 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:August 2019
Deposited On:17 Oct 2019 07:49
Last Modified:18 Feb 2020 11:38
Publisher:Springer
ISSN:0033-3158
Additional Information:This is a post-peer-review, pre-copyedit version of an article published in Psychopharmacology. The final authenticated version is available online at: https://doi.org/10.1007/s00213-019-05315-y
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/s00213-019-05315-y
PubMed ID:31286156

Download

Closed Access: Download allowed only for UZH members

Content: Accepted Version
Language: English
Filetype: PDF - Registered users only until 1 August 2020
Size: 711kB
View at publisher
Embargo till: 2020-08-01