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Title [sv]
Peptiderga mekanismer vid utveckling av drogberoende och av betydelse för relevanta behandlingsstrategier
Title [en]
Peptidergic mechanisms involved in the development of drug dependence and of significance for therapeutical strategies
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 of alcohol and increase the response to stimulants and opiates. We study the mechanism by which AAS affect the actual peptides by examining enzymes controlling their levels but also the mechanism by which AAS interact at receptor level. A particular focus is directed to interactions between AAS and neurosteroids. SP has a recognized role in opiate dependence. Its enhanced effect on opiate 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 synthesized and shown to potently and dose-dependently attenuate withdrawal in morphine tolerant rats. Opiates are also shown to inhibit neurogenesis in hippocampus to induce cognitive deficits. We study the impact of the GH/IGF-1 axis in restoration of opiate 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. This finding opened for similar in vivo studies now going on in our laboratory.
Principal InvestigatorNyberg, Fred
Coordinating organisation
Uppsala University
Funder
Period
2009-01-01 - 2011-12-31
Identifiers
DiVA, id: project:3423Project, id: 2008-03151_VR

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