Motivation and Cerebellar Morphology are Aberrant in a Rodent Model of ADHD

Mentor 1

Rodney Swain

Mentor 2

Amanda Nazario

Start Date

16-4-2021 12:00 AM

Description

Attention Deficit Hyperactivity Disorder (ADHD), a neurobehavioral disorder commonly diagnosed in childhood, is characterized by three core behavioral deficits; hyperactivity, inattention, and impulsivity. These deficits significantly hinder the daily functioning of those diagnosed, both in childhood and adulthood. A less characterized but recognized deficit of those with ADHD concerns difficulties with motivation, with affected persons often requiring larger, more frequent rewards to complete a task. Etiology of the disorder is largely unknown, however, we do know that various areas of the brain, including the cerebellum, have associated abnormalities which warrant further investigation. In this study, we used the Spontaneously Hypertensive Rat (SHR), a rodent model of ADHD that exhibits the three core deficits of the disorder. The goal of this study was to further validate the SHR as a model of ADHD by training rats in an operant conditioning breakpoint paradigm to investigate motivation, and to evaluate possible associated brain abnormalities. Forty-eight male rats, split into SHR and WKY cohorts, were trained on a Progressive Ratio operant schedule that increased in difficulty until the rats reached their breakpoint, which was defined as the point at which the animals stop working for reinforcement. The breakpoint served as a measure of motivation, with a lower breakpoint indicating that the animals had poorer motivation. Results show that the SHR animals had a significantly lower breakpoint compared to the control animals and were thus less motivated to work for reinforcement. These findings add to the behavioral validity of the SHR ADHD model. Unbiased stereological analyses of cerebellar morphology indicated that the volume of both cerebellar vermis and the dentate nucleus were reduced although neuron counts were only lower in lobule 8 of the vermis. These results suggest a likely neurological abnormality underlying the observed behavioral deficits.

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Apr 16th, 12:00 AM

Motivation and Cerebellar Morphology are Aberrant in a Rodent Model of ADHD

Attention Deficit Hyperactivity Disorder (ADHD), a neurobehavioral disorder commonly diagnosed in childhood, is characterized by three core behavioral deficits; hyperactivity, inattention, and impulsivity. These deficits significantly hinder the daily functioning of those diagnosed, both in childhood and adulthood. A less characterized but recognized deficit of those with ADHD concerns difficulties with motivation, with affected persons often requiring larger, more frequent rewards to complete a task. Etiology of the disorder is largely unknown, however, we do know that various areas of the brain, including the cerebellum, have associated abnormalities which warrant further investigation. In this study, we used the Spontaneously Hypertensive Rat (SHR), a rodent model of ADHD that exhibits the three core deficits of the disorder. The goal of this study was to further validate the SHR as a model of ADHD by training rats in an operant conditioning breakpoint paradigm to investigate motivation, and to evaluate possible associated brain abnormalities. Forty-eight male rats, split into SHR and WKY cohorts, were trained on a Progressive Ratio operant schedule that increased in difficulty until the rats reached their breakpoint, which was defined as the point at which the animals stop working for reinforcement. The breakpoint served as a measure of motivation, with a lower breakpoint indicating that the animals had poorer motivation. Results show that the SHR animals had a significantly lower breakpoint compared to the control animals and were thus less motivated to work for reinforcement. These findings add to the behavioral validity of the SHR ADHD model. Unbiased stereological analyses of cerebellar morphology indicated that the volume of both cerebellar vermis and the dentate nucleus were reduced although neuron counts were only lower in lobule 8 of the vermis. These results suggest a likely neurological abnormality underlying the observed behavioral deficits.