Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Strasser, J.
Neurobiological changes associated with addiction with special reference to benzodiazepine dependence
Humanmedizin; [ Diplomarbeit ] Medical University of Graz; 2021. pp. 90
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Holzer Ulrike
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- Abstract:
- Introduction: Benzodiazepines are frequently prescribed as treatment for various disorders such as anxiety, insomnia or convulsive disorders. Unfortunately, they display a risk for adverse events including development of addiction. This thesis summarizes the current knowledge on benzodiazepines, addiction in general and addiction to benzodiazepines in particular. Methods: This diploma thesis is based on a thorough literature research that was conducted via Pubmed using MeSH Terms. Papers were selected via three steps: title-based, abstract-based, and full-text-based. Additionally, a great extent of the literature was acquired by searching the references of the already selected papers and looking for newer articles referencing the originally chosen ones. Results: Addictive drugs are able to activate and hijack the brain’s reward system, in which the ventral tegmental area, the nucleus accumbens, the amygdala and different parts of the prefrontal cortex play an important role. Alterations in these areas on cellular as well as circuit level can be detected after use of addictive drugs. These changes are accompanied by behaviour patterns that can be categorized in three stages: reward-driven use, habit-driven use and compulsive use. Regarding benzodiazepine addiction, there is already some knowledge about the first stage of addiction. Benzodiazepines indirectly lead to an activation of the reward circuit by disinhibiting dopamine neurons in the ventral tegmental area and lead to addiction-related alterations such as modification of the AMPA/NMDA ratio or insertion of GluA2-lacking AMPA receptors at synaptic sites within the VTA. Additionally, the α1 and α2 subunits of the GABA(A)-receptors as binding site for benzodiazepines play an important role in their addictive potential. Discussion: Current scientific knowledge on the addictive properties of benzodiazepines suggests some possibilities to develop new substances without or at least with reduced addictive potential. It would be favourable to spare the involved GABAA-receptor subunits in the binding profile of future substances. Attempts to design such compounds have already been made and some have progressed into clinical development, albeit none are available on the pharmacological market yet. However, there is almost no knowledge on the second and third stage of addiction to benzodiazepines, keeping development of new substances difficult. Further research in this field is crucial for the achievement of addiction-free benzodiazepines.