Supervisors: dr hab. Tomasz Błasiak, prof. UJ (tomasz.blasiak@uj.edu.pl)

Institute of Zoology and Biomedical Research

Background information:

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by impaired attention, increased impulsivity, and hyperactivity. Our current knowledge, both about the symptoms and the neurobiological basis of ADHD, is largely based on clinical and basic research conducted on males. However, there is a growing body of evidence suggesting that both the occurrence and the intensity of some disease symptoms are gender-dependent 1. Moreover, recent research has highlighted a bias in ADHD diagnostic criteria, predominantly derived from male-centric studies, that potentially leads to overlooking the occurrence of diverse symptoms in females. Consequently, women are frequently underdiagnosed, misdiagnosed, or diagnosed later in life.

Unfortunately, the scarcity of neurobiological and behavioural studies conducted on female animal models of ADHD makes it impossible to ascertain whether intersex differences in symptoms are also present in species other than humans. Furthermore, since we do not have knowledge about the neurobiological basis of this disorder in females, it is impossible to compare it with the phenomena observed in males, let alone explain what could be the basis for potential differences in symptoms. One of the significant etiological bases of ADHD, described in males of various species, is the disturbance of neuronal activity control in the prefrontal cortex, especially the right hemisphere of the brain, by catecholaminergic systems: dopaminergic and noradrenergic. The prefrontal cortex plays a key role in attention processes, decision-making, action planning, and emotion control, with the right hemisphere strongly specializing in behavioural inhibition.

Interference in the development of catecholaminergic systems in the neonatal period, involving intracerebroventricular administration of 6-hydroxydopamine, is an animal model of ADHD, although its detailed characterization and thorough validation has been largely conducted on rat and mice males2. The 6‐OHDA animals exhibited the major ADHD‐like symptoms mentioned above, as well as numerous co-existing symptoms including elevated anxiety, antisocial behaviours, and impaired cognitive functions. At the same time, a decrease in amount of catecholamines and structural changes in cortical areas were observed in the animals studied. Furthermore, it was found that most symptoms disappeared under the influence of methylphenidate - a treatment effectively used in humans with ADHD. All of the above has been shown on several species of animals, but mainly on males...

The main question to be addressed in the project:

The primary objectives of the proposed doctoral research involve verifying and validating the aforementioned animal model of ADHD in female rats. Specifically, the behavioural symptoms exhibited by both male and female rats, which serve as an animal model of ADHD, will be compared. Additionally, the study will describe and compare intersex differences in catecholamine release within selected brain areas, such as the prefrontal cortex, in these model animals.

Information on the methods/description of work:

All studies will be conducted on animals - rats, which are the aforementioned model of ADHD, as well as on control animals. The symptoms of the disorder under investigation will be assessed based on observations of animals in behavioral tests, such as open-field, elevated plus-maze, T-maze, novel object recognition, or social interaction tests. Changes in the release of catecholamines (dopamine and norepinephrine) will be imaged in selected brain areas (e.g., prefrontal cortex) in both anesthetized and freely moving animals, using fiber photometry technique.

Additional information (e.g Special requirements from the student):

Applicants should possess experience in conducting in vivo experiments on rodents. This includes proficiency in stereotaxic surgeries, imaging neuronal activity, and behavioral testing. Additionally, candidates should be adept at processing and analyzing the data derived from these experiments.

Place/name of potential foreign collaborator:

Not applicable.

References: