TY - JOUR

T1 - Sequential reversal learning

T2 - a new touchscreen schedule for assessing cognitive flexibility in mice

AU - Odland, Anna U.

AU - Sandahl, Rune

AU - Andreasen, Jesper T.

PY - 2020

Y1 - 2020

N2 - Rationale The widespread deficits in cognitive flexibility observed across psychiatric disorders call for improved rodent tests to understand the biology of cognitive flexibility and development of better psychotherapeutics. Current reversal learning paradigms have a forced-choice setup that challenges the interpretation of results. Objectives We aimed at developing a free-choice reversal learning test, where images are presented sequentially and animals are free to move, to enable investigation of the cognitive sub-processes that occur during reversal. Methods Behavior in female C57BL/6JOlaHsd mice was characterized using chronic fluoxetine as a reference compound. Additional tests were included to support the interpretation of results and exclude confounding pharmacological effects. Behaviors in vehicle-treated mice were furthermore analyzed for relatedness to deepen the understanding of parameters measured. Results We found that exploitation of the previously rewarded image was independent of exploration and acquisition of the new reward contingency and could be differentially modulated by fluoxetine, supporting recent theories that these processes are not mutually exclusive. Specifically, fluoxetine reduced mistake rate, premature and perseverative responses, and promoted conservative strategies during reversal without affecting hit rate. These effects appeared to be most prominent during the late stage of reversal learning, where accuracy was above chance level. Analysis of behaviors in vehicle-treated mice suggested that exploitation was related to an impulsive-like deficit in response inhibition, while exploration was more related to motivation. Conclusions This new schedule was feasible, easy to implement, and can provide a deeper understanding of the cognitive sub-processes during reversal.

AB - Rationale The widespread deficits in cognitive flexibility observed across psychiatric disorders call for improved rodent tests to understand the biology of cognitive flexibility and development of better psychotherapeutics. Current reversal learning paradigms have a forced-choice setup that challenges the interpretation of results. Objectives We aimed at developing a free-choice reversal learning test, where images are presented sequentially and animals are free to move, to enable investigation of the cognitive sub-processes that occur during reversal. Methods Behavior in female C57BL/6JOlaHsd mice was characterized using chronic fluoxetine as a reference compound. Additional tests were included to support the interpretation of results and exclude confounding pharmacological effects. Behaviors in vehicle-treated mice were furthermore analyzed for relatedness to deepen the understanding of parameters measured. Results We found that exploitation of the previously rewarded image was independent of exploration and acquisition of the new reward contingency and could be differentially modulated by fluoxetine, supporting recent theories that these processes are not mutually exclusive. Specifically, fluoxetine reduced mistake rate, premature and perseverative responses, and promoted conservative strategies during reversal without affecting hit rate. These effects appeared to be most prominent during the late stage of reversal learning, where accuracy was above chance level. Analysis of behaviors in vehicle-treated mice suggested that exploitation was related to an impulsive-like deficit in response inhibition, while exploration was more related to motivation. Conclusions This new schedule was feasible, easy to implement, and can provide a deeper understanding of the cognitive sub-processes during reversal.

KW - Touchscreen

KW - Cognitive flexibility

KW - Reversal learning

KW - Mouse behavior

KW - Serotonin

KW - Exploitation

KW - Exploration

KW - Extinction

KW - Sequential

KW - Go

KW - no-go

KW - CHRONIC FLUOXETINE TREATMENT

KW - INTERMITTENT COLD STRESS

KW - ORBITOFRONTAL CORTEX

KW - EXECUTIVE FUNCTION

KW - OPERANT PLATFORM

KW - SEROTONIN

KW - DYSFUNCTION

KW - TASK

KW - RATS

KW - GO

U2 - 10.1007/s00213-020-05687-6

DO - 10.1007/s00213-020-05687-6

M3 - Journal article

C2 - 33123820

VL - 238

SP - 383

EP - 397

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

ER -