Characterisation of a touchscreen-based task for assessing cognitive judgement bias in mice: a new translational tool for affective state disorder drug screening

Abstract

Rationale A major obstacle in the pre-clinical study of mood-related disorders and novel affective state therapeutic evaluation is the lack of animal models that fully recapitulate human symptomatology. Objective In this study, we developed a touchscreen-based cognitive judgement bias (CJB) task for mice. Methods In the CJB task, animals first learned to discriminate between two visual stimuli displayed on the touchscreen: one associated with a reward (S+) and one associated with a time-out and flashing house light (S-). Once mice learned to respond to the S + and to withhold responding to the S- consistently, a set of four ambiguous stimuli ranging in visual similarity to the S + and S- stimuli were randomly interspersed in the stimulus presentation sequence. Responses to these ambiguous stimuli were interpreted as a greater expectation of positive (‘optimistic bias’) or negative (‘pessimistic bias’) outcomes as a function of their similarity to the S + or S- stimuli. Results The acute administration of the SSRIs fluoxetine and citalopram, and the 5HT-2 C receptor antagonist SB 242084, did not produce any effects on CJB task performance. However, the noradrenaline/dopamine reuptake inhibitor, bupropion, increased responses to the ambiguous stimuli consistent with the induction of an ‘optimistic bias’, and the pro-depressant tetrabenazine yielded the opposite effect. Conclusion This study underscores the capacity of mice to respond to visually ambiguous stimuli in an ambiguity-dependent manner, a phenomenon observed across various species, including humans. Furthermore, it establishes and validates an operant behavioural task to assess CJB in mice delivered using the touchscreen platform, which has significant cross-species translational potential.

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