Mouse psychosocial stress reduces motivation and cognitive function in operant reward tests: A model for reward pathology with effects of agomelatine

TY - JOUR

T1 - Mouse psychosocial stress reduces motivation and cognitive function in operant reward tests

T2 - A model for reward pathology with effects of agomelatine

AU - Bergamini, Giorgio

AU - Cathomas, Flurin

AU - Auer, Sandra

AU - Sigrist, Hannes

AU - Seifritz, Erich

AU - Patterson, Michael

AU - Gabriel, Cecilia

AU - Pryce, Christopher R

N1 - Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

PY - 2016/9/26

Y1 - 2016/9/26

N2 - A major domain of depression is decreased motivation for reward. Translational automated tests can be applied in humans and animals to study operant reward behaviour, aetio-pathophysiology underlying deficits therein, and effects of antidepressant treatment. Three inter-related experiments were conducted to investigate depression-relevant effects of chronic psychosocial stress on operant behaviour in mice. (A) Non-manipulated mice were trained on a complex reversal learning (CRL) test with sucrose reinforcement; relative to vehicle (VEH), acute antidepressant agomelatine (AGO, 25mg/kg p.o.) increased reversals. (B) Mice underwent chronic social defeat (CSD) or control handling (CON) on days 1-15, and were administered AGO or VEH on days 10-22. In a progressive ratio schedule motivation test for sucrose on day 15, CSD mice made fewer responses; AGO tended to reverse this effect. In a CRL test on day 22, CSD mice completed fewer reversals; AGO tended to increase reversals in CSD mice associated with an adaptive increase in perseveration. (C) Mice with continuous operant access to water and saccharin solution in the home cage were exposed to CSD or CON; CSD mice made fewer responses for saccharin and water and drank less saccharin in the active period, and drank more water in the inactive period. In a separate CSD cohort, repeated AGO was without effect on these home cage operant and consummatory changes. Overall, this study demonstrates that psychosocial stress in mice leads to depression-relevant decreases in motivation and cognition in operant reward tests; partial reversal of these deficits by AGO provides evidence for predictive validity.© 2016, Elsevier B.V. and ECNP. The attached document (embargoed until 13/07/2017) is an author produced version of a paper published in European Neuropsychopharmacology, uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at https://doi.org/10.1016/j.euroneuro.2016.06.009. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

AB - A major domain of depression is decreased motivation for reward. Translational automated tests can be applied in humans and animals to study operant reward behaviour, aetio-pathophysiology underlying deficits therein, and effects of antidepressant treatment. Three inter-related experiments were conducted to investigate depression-relevant effects of chronic psychosocial stress on operant behaviour in mice. (A) Non-manipulated mice were trained on a complex reversal learning (CRL) test with sucrose reinforcement; relative to vehicle (VEH), acute antidepressant agomelatine (AGO, 25mg/kg p.o.) increased reversals. (B) Mice underwent chronic social defeat (CSD) or control handling (CON) on days 1-15, and were administered AGO or VEH on days 10-22. In a progressive ratio schedule motivation test for sucrose on day 15, CSD mice made fewer responses; AGO tended to reverse this effect. In a CRL test on day 22, CSD mice completed fewer reversals; AGO tended to increase reversals in CSD mice associated with an adaptive increase in perseveration. (C) Mice with continuous operant access to water and saccharin solution in the home cage were exposed to CSD or CON; CSD mice made fewer responses for saccharin and water and drank less saccharin in the active period, and drank more water in the inactive period. In a separate CSD cohort, repeated AGO was without effect on these home cage operant and consummatory changes. Overall, this study demonstrates that psychosocial stress in mice leads to depression-relevant decreases in motivation and cognition in operant reward tests; partial reversal of these deficits by AGO provides evidence for predictive validity.© 2016, Elsevier B.V. and ECNP. The attached document (embargoed until 13/07/2017) is an author produced version of a paper published in European Neuropsychopharmacology, uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at https://doi.org/10.1016/j.euroneuro.2016.06.009. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

U2 - 10.1016/j.euroneuro.2016.06.009

DO - 10.1016/j.euroneuro.2016.06.009

M3 - Article

C2 - 27422761

SN - 0924-977X

VL - 26

SP - 1448

EP - 1464

JO - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

IS - 9

ER -