Assessment of impulsivity in adolescent mice: A new training procedure for a 3-choice serial reaction time task

Abstract

Immaturity in impulse control among adolescents could result in substance abuse, criminal involvement, and suicide. The brains of adolescents and adults are anatomically, neurophysiologically, and pharmacologically different. Therefore, preclinical models of adolescent impulsivity are required to screen drugs for adolescents and elucidate the neural mechanisms underlying age-related differences in impulsivity. The conventional 3- or 5-choice serial reaction time task, which is a widely used task to assess impulsivity in adult rodents, cannot be used for young mice because of two technical problems: impaired growth caused by food restriction and the very long training duration. To overcome these problems, we altered the conventional training process, optimizing the degree of food restriction for young animals and shortening the training duration. We found that almost all basal performance levels were similar between the novel and conventional procedures. We also confirmed the pharmacological validity of our results: the 5-hydroxytryptamine 2C (5-HT) receptor agonist Ro60-0175 (0.6 mg/kg, subcutaneous) reduced the occurrence of premature responses, whereas the 5-HT receptor antagonist SB242084 (0.5 mg/kg intraperitoneal) increased their occurrence, consistent with results of previous studies using conventional procedures. Furthermore, we detected age-related differences in impulsivity using the novel procedure: adolescent mice were found to be more impulsive than adult mice, congruent with the results of human studies. Thus, the new procedure enables the assessment of impulsivity in adolescent mice and facilitates a better understanding of the neurophysiological/pharmacological properties of adolescents.

DIY-NAMIC Behavior: A High-Throughput Method to Measure Complex Phenotypes in the Homecage

“…This may suggest a more challenging task which may have obscured age differences. On the other hand, our results were consistent with another previous report of impulsivity measured in adolescent mice using a modified training procedure for 3-CSRTT in a traditional session-based design in commercial equipment (Sasamori et al, 2018). These authors report increased impulsive action in late adolescent mice as measured increased by premature responses, however did not see increased omissions as seen in our data.…”

“…Do-it-yourself (DIY) operant behavioral testing apparatus have been developed for use with standard session-based testing methods which provide relatively inexpensive and customizable apparatus making behavioral testing more accessible ( Devarakonda et al, 2016 ). Additionally, there have been modifications to traditional commercial equipment, and also to standard lengthy paradigms making shorter training times possible ( Remmelink et al, 2017 ; Sasamori et al, 2018 ). What was still lacking, however, was a method that combined these advantages to allow for both homecage and continuous assessment of operant behavior, with liquid reward in an affordable open-source system.…”

The effects of violent video games and shyness on individuals’ aggressive behaviors

“…A large number of studies have used the CRTT to test the influences of VVGs on individuals’ aggressive behaviors (Anderson et al, ; Sasamori, Ohmura, Kubo, Yoshida, & Yoshioka, ). In recent years, an increasing number of studies have used the modified CRTT (MCRTT) which uses noise blasts for punishment rather than electric shocks (Sasamori et al, ). Various versions of this task have shown good internal validity (Hyatt, Chester, Zeichner, & Miller, ; Warburton, & Bushman, ).…”

DIY-NAMIC behavior: A high-throughput method to measure complex phenotypes in the homecage

“…Some of these studies have taken the strategy of eliminating mice that don't learn quickly enough to progress to increasingly complex behavioral paradigms, leading to potentially biased samples [45]. There has also been some progress in the development of new training paradigms that reduce training time to allow testing in adolescent mice [38,46], however they still require food deprivation which could be detrimental to growth and the maturation of feeding circuits during the adolescence. Inexpensive Arduino-based operant testing apparatus have also been developed, such as ROBucket [37], though these have also been used with the daily experimenter-initiated daily sessions.…”

“…'do-it-yourself' (DIY) operant behavioral testing apparatus have been developed for use with standard session-based testing methods which provide relatively inexpensive and customizable apparatus making behavioral testing more accessible [37]. Additionally, there have been modifications made to traditional commercial equipment, and also to standard lengthy paradigms making shorter training times possible [38,39]. What was still lacking, however, was a method that combined these advantages to allow for both homecage and continuous assessment of operant behavior, with liquid reward in an affordable open-source system.…”