Oberrauch, S;
Sigrist, H;
Sautter, E;
Gerster, S;
Bach, DR;
Pryce, CR;
(2019)
Establishing operant conflict tests for the translational study of anxiety in mice.
Psychopharmacology
, 236
(8)
pp. 2527-2541.
10.1007/s00213-019-05315-y.
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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.
| Type: | Article |
|---|---|
| Title: | Establishing operant conflict tests for the translational study of anxiety in mice |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00213-019-05315-y |
| Publisher version: | https://doi.org/10.1007/s00213-019-05315-y |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Neurosciences, Pharmacology & Pharmacy, Psychiatry, Neurosciences & Neurology, Anxiety, Reward-aversion conflict, Translational test, Mouse, Operant choice, Response latency, Response vigour, Anxiolytic, ELEVATED PLUS-MAZE, ANIMAL-MODELS, HIPPOCAMPUS, CIRCUITS, AGONIST, RODENT, FEAR |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10090433 |
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