Einfluss von chronischer THC-Gabe auf den zerebralen Glukosemetabolismus in weiblichen C57BL/6-Mäusen

by Daniel Günther
Doctoral thesis
Date of Examination:2024-07-25
Date of issue:2024-07-25
Advisor:PD Dr. Yvonne Bouter
Referee:PD Dr. Yvonne Bouter
Referee:Prof. Dr. Caroline, Bouter
Persistent Address: http://dx.doi.org/10.53846/goediss-10623

 

 

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Abstract

English

Cannabis is the most widely consumed recreational drug in the world and is also becoming increasingly relevant in the medical sector with promising pharmacological effects. THC interacts with the endocannabinoid system, which plays a crucial role in brain development, learning, memory, anxiety, behavior, neuroprotection, and plasticity, particularly through the CB1 receptor. Studies show that cannabis use can be associated with increased risks of mental health disorders and cognitive impairments. This study aims to assess the impact of chronic THC consumption on cerebral metabolism in healthy female C57BL/6 mice using 18F-FDG-PET imaging. Mice were divided into two age groups: " young" (seven months) and "old" (twelve months). Both groups received high-dose THC (20 mg/kg) intraperitoneally over the course of 42 days. A third group, "young abstinent THC," received THC at three months old followed by a two-month abstinence. With this third group, behavioral experiments were conducted to detect persistent cerebral effects post-abstinence and before PET-Imaging at the age of 7 months. Imaging results showed significant reductions in brain activity across all examined regions in the "young" mice after chronic THC exposure. The "young abstinent THC" group exhibited the lowest cerebral glucose uptake, indicating persistent effects despite abstinence. Behavioral tests of the third group suggested compensatory mechanisms, as no learning, anxiety, or motor deficits were observed. In contrast, "old" mice showed no significant changes except in the amygdala, suggesting age-dependent neuroadaptation and tolerance. Overall, this study demonstrates, that chronic THC exposure significantly affects the brains metabolism of young mice. These effects persist despite prolonged abstinence, without affecting the behaviour of the mice.
Keywords: Cannabis; THC; FDG-PET; Behavior testing