The dynamic strategy shifting task: Optimisation of an operant task for assessing cognitive flexibility in rats

Front Psychiatry. 2024 Jun 28:15:1303728. doi: 10.3389/fpsyt.2024.1303728. eCollection 2024.

Abstract

Introduction: Although schizophrenia is associated with a broad range of symptoms including hallucinations, delusions, and reduced motivation, measures of cognitive dysfunction, including cognitive flexibility and executive function, are the strongest predictors of functional outcomes. Antipsychotic medications are useful for reducing psychotic symptoms, but they are ineffective at improving cognitive deficits. Despite extensive investment by industry, the transition from preclinical to clinical trials has not been successful for developing precognitive medications for individuals with schizophrenia. Here, we describe the optimisation of a novel dynamic strategy shifting task (DSST) using standard operant chambers to investigate the optimal stimuli required to limit the extensive training times required in previous tasks.

Methods: We determined that optimal learning by male and female Sprague Dawley rats for the flexibility task incorporated dynamic strategy shifts between spatial rules, such as following a visual cue or responding at one location, and non-spatial rules, such as responding to a central visual or auditory cue. A minimum of 6 correct consecutive responses were required to make a within-session change in the behavioural strategies. As a proof of concept, we trained and tested 84 Sprague Dawley rats on the DSST, and then assessed their cognitive flexibility using a within-subject design after an acute dose of ketamine (0, 3, 10 mg/kg). Rats made fewer premature and more perseverant responses to initiate a trial following ketamine. The effects of ketamine on trials to criterion was dependent on the rule.

Results: Ketamine induced a significant improvement on the reversal of a non-spatial visual discrimination rule. There was no significant effect of ketamine on the spatial visual or response discrimination rules.

Discussion: The DSST is a novel assay for studying distinct forms of cognitive flexibility and offers a rapid and adaptable means of assessing the ability to shift between increasingly challenging rule conditions. The DSST has potential utility in advancing our understanding of cognitive processes and the underlying neurobiological mechanisms related to flexibility in neuropsychiatric and neurological conditions where executive dysfunctions occur.>.

Keywords: cognitive flexibility; neuropsychiatric disease; operant tasks; strategy-shifting; translational research.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. JF was supported by an Australian Government Research Training Program Scholarship, and top-up funding was provided through the Queensland Brain Institute, University of Queensland. This research was supported from core funding from the Queensland Centre for Mental Health Research and grants from National Health and Medical Research Council (APP1078159, APP1099709 and 2020567) awarded to TB.