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Nandrolone decanoate administration elevates hippocampal prodynorphin mRNA expression and impairs Morris water maze performance in male rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Bakalkin)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
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2009 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 467, no 3, 189-193 p.Article in journal (Refereed) Published
Abstract [en]

The misuse of anabolic androgenic steroids has in several reports been associated with effects resulting in altered behavior and cognition. This study used the Morris water maze task to investigate the effect of high doses of the anabolic androgenic steroid nandrolone on spatial learning and memory in male rats. The results on day two of the experiment and during the final probe trial indicated significant memory impairment compared with controls. The hippocampus, a brain region associated with cognitive function, was analyzed for mRNA expression of prodynorphin, the precursor of dynorphinergic peptides. The results indicated that the transcription levels of prodynorphin were significantly elevated in the animals treated with nandrolone compared with controls. Thus, the findings suggest that administration of nandrolone to male rats impairs memory function, possibly via dynorphinergic actions.

Place, publisher, year, edition, pages
2009. Vol. 467, no 3, 189-193 p.
Keyword [en]
Anabolic androgenic steroids (AAS), Learning and memory, Morris water maze, Rat, Prodynorphin, TaqMan PCR
National Category
Pharmaceutical Sciences
Research subject
Biological Research on Drug Dependence
Identifiers
URN: urn:nbn:se:uu:diva-107477DOI: 10.1016/j.neulet.2009.09.041ISI: 000272517600002PubMedID: 19782718OAI: oai:DiVA.org:uu-107477DiVA: diva2:231405
Available from: 2009-08-12 Created: 2009-08-12 Last updated: 2017-12-13Bibliographically approved
In thesis
1. The Impact of Nandrolone Decanoate on Neuropeptidergic Mechanisms Related to Cognition, Aggression, Reward and Dependence
Open this publication in new window or tab >>The Impact of Nandrolone Decanoate on Neuropeptidergic Mechanisms Related to Cognition, Aggression, Reward and Dependence
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The abuse of anabolic androgenic steroids (AAS) is becoming increasingly common and may result in a range of physiological as well as psychological effects such as altered behavior in terms of increased aggression, cognitive dysfunction and addictive behavior. AAS comprise testosterone and its derivatives, of which nandrolone is one of the more common. Previous studies have shown nandrolone-induced effects in male rats on peptide levels within the Substance P (SP) system and the dynorphinergic system; these effects may be linked to some of the reported behavior alterations. The studies presented in this thesis aimed to investigate the mechanisms underlying these peptide alterations and also to further investigate neuropeptidergic effects attributed to nandrolone administration. The results display significant effects on the enzymatic conversion of SP and Dynorphin A into their bioactive metabolites SP(1-7) and Leu-enkephalin-Arg6, respectively, as a result of nandrolone treatment. More profound investigations on the dynorphinergic system displayed effects on the kappa opioid receptor density in various brain regions. There was also a significant increase in the expression of the gene transcript of prodynorphin in the hippocampus, a brain region associated with cognitive processes. In addition, impaired spatial learning and memory in the Morris water maze task following nandrolone administration was encountered. The results provide further understanding regarding neuropeptidergic mechanisms underlying AAS-induced behavioral effects.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 103
Keyword
Anabolic androgenic steroids, Nandrolone decanoate, Substance P, Dynorphin A, KOP receptor, Prodynorphin, Radioimmunoassay, Autoradiography, Morris water maze, PCR, Central nervous system
National Category
Pharmacology and Toxicology
Research subject
Biological Research on Drug Dependence
Identifiers
urn:nbn:se:uu:diva-107483 (URN)978-91-554-7587-1 (ISBN)
Public defence
2009-09-25, B42, BMC, Husargatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2009-09-03 Created: 2009-08-12 Last updated: 2011-05-05Bibliographically approved

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Hånell, AndersBazov, Igor

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