Interaction between CB1 receptor availability, glucose uptake and rate limiting steps of neuronal metabolism in an animal model of ADHD

• Applicants: Professorin Dr. Parvana Hajieva; Privatdozentin Dr. Isabelle Miederer
• Subject Area: Biological Psychiatry ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544482604

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with core symptoms of attention deficit, hyperactivity, and impulsivity. At the neurotransmitter level, the dopaminergic and noradrenergic systems are thought to be involved in the pathogenesis of ADHD, while an involvement of the serotonergic system is also conceivable. In addition, recent studies increasingly assign a key role to the endocannabinoid system in the expression of ADHD. In addition to the question of the involvement of these neurotransmitter systems in the onset and development of ADHD, there is ongoing debate as to whether ADHD is in fact a neuroenergetic disorder originating in an insufficient energy supply which subsequently leads to an insufficient release of neurotransmitters (such as dopamine) and ultimately to inadequate neurotransmission. For the study of ADHD, the spontaneously hypertensive rat (SHR) model has been validated as an animal model. Using this animal model, we aim to shed further light on the neural mechanisms underlying ADHD that are not yet fully understood.In this study, we refer to the ADHD core symptom "impulsivity" mediated by a fronto-striatal network; in view of the fact that we are, more specifically, investigating the "waiting impulsivity" component, the ventral striatum will assume particular importance. The ground-breaking aspect of this study is that the CB1 receptor availability in this area has never before been investigated with the aid of an ADHD rat model. Further analyses will examine correlations between CB1 availability and neuronal activity in fronto-striatal brain regions, as well as correlations between CB1 availability (in these brain regions) and impulse control. In addition, changes in rate-limiting steps of energy metabolism in fronto-striatal brain regions will be examined. Finally, in view of the number of ADHD patients using cannabis-based products for medicinal purposes, we see the investigation of the effects of tetrahydrocannabinol (THC) at the neuronal level and the underlying metabolic pathways as an imperative element of this study.The results will allow us to expose the underlying mechanisms of disease-specific changes in CB1 receptor availability, neuronal activity ([18F]FDG uptake), and rate-limiting steps of energy metabolism under basal conditions and THC treatment.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Mathias Schreckenberger