Ramiz M. Salimov, Natalia А. Sukhorukova, Georgy I. Kovalev

Comparison of CD-1 and ICR mouse strains for impulsivity in the enriched cross-maze test: Effects of atomoxetine

Introduction

Comparison of cd-1 and icr mouse strains for impulsivity in the enriched cross-maze test: effects of atomoxetine. Compare CD-1 & ICR mouse impulsivity in an enriched cross-maze, testing atomoxetine for ADHD treatment. Reveals impulsivity subpopulations and atomoxetine's selective effects.

Abstract

Introduction: Attention deficit hyperactivity disorder (ADHD) in children and adults is a neuropsychiatric condition that is characterized by difficulty sustaining attention and behavioral impulsivity. It is one of the problems of modern medicine requiring development of appropriate treatments and valid animal models. Previously, we have developed a model of the enriched cross-maze test suitable for express-evaluation of attention deficiency in rodents. Recently, we have also revealed that while employing spontaneously hypertensive rats it is possible to estimate impulsivity indices in the test. The present study is aimed at evaluation of the impulsivity indicators in the enriched cross-maze test employing mice of outbred CD-1 and ICR strains, belonging to different breeding cores. Materials and Method: Adult male mice of the both outbred CD-1 (n=199) and ICR (n=148) strains were used in the study. Atomoxetine (3 mg/kg) as the drug of choice for ADHD was administered intraperitoneally once daily for 6 consecutive days. Results and Discussion: Frequency distribution of the impulsivity index obtained from mice of both strains had a clear bimodal shape that statistically significantly differed from the normal distribution. The outcome indicates existence of subpopulations of individuals with high and low impulsivity. In inattentive mice, the subchronic atomoxetine administration selectively improved impulsivity indicators in the second enriched cross-maze test. Conclusion: The enriched cross-maze test may be useful in neurobiology studies of ADHD and for screening new drug candidates for the ADHD treatment.

Review

This study presents an intriguing initial exploration into characterizing impulsivity in CD-1 and ICR mouse strains using an enriched cross-maze test, with a focus on its sensitivity to atomoxetine, a drug used for ADHD. The research addresses a pertinent need for valid animal models of ADHD, particularly concerning the often-complex interplay of attention and impulsivity. A notable strength is the discovery of a bimodal distribution of impulsivity indices, suggesting the existence of distinct subpopulations of high and low impulsivity within these outbred strains. This finding could have significant implications for understanding individual variability in ADHD-like traits and for designing more targeted preclinical studies. Furthermore, the selective improvement of impulsivity indicators by atomoxetine in "inattentive mice" provides promising pharmacological validation for the utility of this test. However, a more comprehensive evaluation is hampered by the abstract's brevity regarding critical methodological details. The precise nature of the "enriched cross-maze test" for measuring impulsivity, including the specific "impulsivity indices" derived, is not elaborated. Given that the test was initially developed for attention and "recently revealed" to estimate impulsivity, clearer operational definitions and a brief description of the task parameters are essential for reproducibility and interpretation. The abstract also introduces the concept of "inattentive mice" within a study primarily focused on impulsivity; clarification on how these "inattentive" individuals were identified and whether their impulsivity profiles were distinct, especially in light of the bimodal distribution, is crucial. While the large sample sizes are commendable, the use of only one dose of atomoxetine limits insights into dose-response relationships. In conclusion, this work lays important groundwork for potentially establishing a valuable rodent model for ADHD-related impulsivity and for screening new therapeutic compounds. The identification of distinct impulsivity subpopulations is a particularly compelling finding that warrants further investigation into its neurobiological and genetic bases. To fully realize its potential, future publications derived from this work should meticulously detail the experimental procedures of the enriched cross-maze test, including specific behavioral measures, and provide a clear framework for defining and differentiating attention and impulsivity within the model. Addressing these points would significantly enhance the study's robustness and contribute meaningfully to the field of ADHD research.

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