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Title [sv]
Pepdiderga mekanismer vid drogberoende och utveckling av strategier för behandling av beroende och återställande av drog-inducerade hjärnskador
Title [en]
Peptidergic mechanism in drug addiction and the development of rational strategies for the treatment of drug addicts and repairements of drug-induced brain damages
Abstract [sv]
Anabolic androgenic steroids (AAS) are shown to induce an imbalance in opioid peptides regulating brain reward and in the substance P (SP) system in areas involved in reward and aggression. Behavioral tests showed that AAS increased intake and response to other abusing drugs. We study the mechanism by which AAS act in this regard and how they interacts with neurosteroids. SP has an enhanced effect on opioid withdrawal is counteracted by its fragment SP(1-7) acting on dopaminergic reward circuits. We identified specific sites for SP(1-7) in the rat CNS distinct from known opioid and SP receptors. SP(1-7) mimetics were shown to potently and dose-dependently attenuate withdrawal in morphine tolerant rats. Opiates as well as alcohol are also shown to inhibit neurogenesis in hippocampus causing cognitive deficits. We study the impact of the GH/IGF-1 axis in restoration of opioid induced impairment in this tissue. We showed that GH enhances cognitive capabilities and we confirmed an interaction between the hormone and the NMDA receptor complex in hippocampus. Now we have successfully shown that GH may reverse opiate induced apoptosis in primary cultures from mouse hippocampus. A similar observation was made in animal in vivo models. Thus, we continue to study the impact of the GH/IGF-1 axis in restoration of opioid-induced damage of the hippocampus but we also perform studies to examine similar effects of GH on damage induced by other drugs of abuse, e.g alcohol and AAS.
Principal InvestigatorNyberg, Fred
Coordinating organisation
Uppsala University
Funder
Period
2012-01-01 - 2014-12-31
National Category
Substance Abuse
Identifiers
DiVA, id: project:4565Project, id: 2011-04579_VR

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