The enriched cross-maze test as a model of impulsivity and attention deficit in spontaneously hypertensive rats
Authors
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Ramiz M. Salimov
https://orcid.org/0000-0002-9297-9847
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Georgy I. Kovalev
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
https://orcid.org/0000-0002-8597-7018
DOI:
https://doi.org/10.18413/rrpharmacology.11.533Abstract
Introduction: Attention deficit hyperactivity disorder (ADHD) is one of the problems of modern medicine, which requires development of appropriate treatments using animal models. One of the valid genetic models of ADHD in animals is the spontaneous hypertensive (SH) outbred rats line. Results of the present paper demonstrate heterogeneity among the SH rats line regarding measures of impulsivity and attention deficit obtained by the use of the enriched cross-maze test and assesses the effects of clinically effective anti-ADHD drug atomoxetine.
Materials and Method: 106 adult male SH outbred rats were used. Their exploratory behavior was assessed in the enriched cross-maze test, which provides correlates of impulsivity and attention to enriching objects regardless of overall motor activity. The device consists of 4-arm radial maze, two arms of which contain objects (enriched compartments). Normal non-impulsive and attentive animals exploring the maze usually spend more time in the central compartment before entering the enriched arms and then spend more time in these arms as compared to when in the empty arms.Impulsive and inattentive individuals have the opposite tendency. Atomoxetine (3 mg/kg) was administered orally, once daily for 4 days.
Results and Discussion: Frequency distribution of the impulsivity index had clear bimodal form, which statistically significantly differed from the normal distribution. The outcome indicates existence of subpopulations of individuals with high and low impulsivity. Subpopulation with high impulsivity and low attention to enriching objects (34% of individuals from experiment 1), which are parallel to patients with ADHD, was collected for experiment 2 in which they were treated with atomoxetine or placebo. Subchronic atomoxetine selectively improved impulsivity and attention measures in the second enriched cross-maze test.
Conclusion: The enriched cross-maze test may be useful in neurobiology studies of impulsivity and attention deficit and for screening new drug candidates.
Graphical Abstract
Keywords:
impulsivity, attention deficit, enriched cross-maze, rats with spontaneous hypertension, AtomoxetineReferences
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