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Title [sv]
Centrala mekanismer vid drogberoende och utveckling av rationella strategier för behandling och återställande av drog-inducerade hjärnskador
Title [en]
Central mechanisms in drug addiction and development of rational strategies for treatment and restoration of drug-induced brain damages
Abstract [sv]
Anabolic androgenic steroids (AAS) have been shown to increase aggression and also to affect the brain reward system. Behavioral tests demonstrate that AAS increase intake and response to other drugs of abuse. In addition to these effects, long-term AAS administration seems to affect cognition both in human and animal models. Previously, we have studied how AAS, but also opiates as well as alcohol inhibit neurogenesis in hippocampus and frontal cortex causing cognitive deficits. In order to restore the drug-induced impairment in these tissues we have studied the impact of the GH/IGF-1 axis. We previously showed that GH enhances cognitive capabilities and confirmed an interaction between the hormone and the NMDA receptor complex in hippocampus. We have now successfully shown that GH may reverse cognitive disabilities in animal in vivo models. Thus, damages induced by AAS and opiates have been reversed by GH treatment. In clinical collaboration we have also extended our study to humans. We recently reported that GH reversed cognitive disabilities seen in a patient previously exposed to opioids. We also use animals to find new routes for GH administration, using gene therapy. In this approach we apply an animal model for delivering GH by administration of an AAVrh.10 gene transfer vector expressing GH and delivering the hormone to the brain. Our preliminary results indicate that the hormone gene may reach its specific brain targets as assessed by immunotechniques.
Principal InvestigatorNyberg, Fred
Coordinating organisation
Uppsala University
Funder
Period
2015-01-01 - 2017-12-31
National Category
Pharmacology and Toxicology
Identifiers
DiVA, id: project:5308Project, id: 2014-03489_VR

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