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The Impact of Nandrolone Decanoate on Neuropeptidergic Mechanisms Related to Cognition, Aggression, Reward and Dependence
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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 [en]
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: urn:nbn:se:uu:diva-107483ISBN: 978-91-554-7587-1 (print)OAI: oai:DiVA.org:uu-107483DiVA: diva2:231439
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
List of papers
1. Nandrolone decanoate administration dose-dependently affects the density of kappa opioid peptide receptors in the rat brain determined by autoradiography
Open this publication in new window or tab >>Nandrolone decanoate administration dose-dependently affects the density of kappa opioid peptide receptors in the rat brain determined by autoradiography
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2009 (English)In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 43, no 2, 105-111 p.Article in journal (Refereed) Published
Abstract [en]

The kappa opioid receptor ligand [(3)H]CI-977 was used to autoradiographically determine the density of kappa opioid receptors in the male rat brain following chronic treatment with the anabolic androgenic steroid nandrolone decanoate at two different doses. As compared to controls, significantly lower densities of the kappa opioid receptor were encountered after two weeks of high dose nandrolone decanoate (15 mg/kg) in the nucleus accumbens shell (16%), lateral hypothalamic area (36%), ventromedial hypothalamic nucleus (37%), dorsomedial hypothalamic nucleus (49%), central amygdaloid nucleus, capsular part (28%), lateral globus pallidus (35%) and in the stria terminalis (24%). Furthermore, an up-regulation of the receptor level was observed in the caudate putamen (18%) and in the dorsal endopiriform nucleus (23%). These alterations in the kappa opioid receptor expression are possibly attributed to a previously observed pronounced impact of nandrolone decanoate on the dynorphinergic system and could also include involvement of the dopaminergic reward system.

Keyword
Anabolic androgenic steroids (AAS), Autoradiography, Kappa opioid peptide receptor (KOP receptor), Rat, Brain
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-104435 (URN)10.1016/j.npep.2008.12.005 (DOI)000265520700006 ()19201466 (PubMedID)
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2012-10-08Bibliographically approved
2. Enzymatic conversion of dynorphin A in the rat brain is affected by administration of nandrolone decanoate
Open this publication in new window or tab >>Enzymatic conversion of dynorphin A in the rat brain is affected by administration of nandrolone decanoate
2007 (English)In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 28, no 4, 851-858 p.Article in journal (Refereed) Published
Abstract [en]

The misuse of anabolic androgenic steroids (AAS) seems to produce profound effects on the central nervous system, leading to aggressive behavior and increased sensitivity to other drugs of abuse. The present study addresses the effect on the enzymatic transformation, here called dynorphin converting enzyme-like activity. The formation of the mu/delta opioid peptide receptor-preferring Leu-enkephalin-Arg6 from the kappa opioid peptide receptor-preferring dynorphin A was measured in rats treated with nandrolone decanoate. Significant variations in enzymatic transformation were observed in several brain regions. An altered receptor activation profile in these regions may be one contributory factor behind AAS-induced personality changes.

Keyword
Anabolic androgenic steroids (AAS), Nandrolone decanoate, Dynorphin converting enzyme, Rat brain, Enzyme, Dynorphin
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-10868 (URN)10.1016/j.peptides.2006.12.011 (DOI)000245625900017 ()17240479 (PubMedID)
Available from: 2007-04-26 Created: 2007-04-26 Last updated: 2011-02-07Bibliographically approved
3. Administration of the anabolic androgenic steroid nandrolone decanoate affects substance P endopeptidase-like activity in the rat brain.
Open this publication in new window or tab >>Administration of the anabolic androgenic steroid nandrolone decanoate affects substance P endopeptidase-like activity in the rat brain.
2006 (English)In: Peptides, ISSN 0196-9781, Vol. 27, no 1, 114-21 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-75670 (URN)16099548 (PubMedID)
Available from: 2006-02-14 Created: 2006-02-14 Last updated: 2011-01-11
4. Nandrolone decanoate administration elevates hippocampal prodynorphin mRNA expression and impairs Morris water maze performance in male rats
Open this publication in new window or tab >>Nandrolone decanoate administration elevates hippocampal prodynorphin mRNA expression and impairs Morris water maze performance in male rats
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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.

Keyword
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:nbn:se:uu:diva-107477 (URN)10.1016/j.neulet.2009.09.041 (DOI)000272517600002 ()19782718 (PubMedID)
Available from: 2009-08-12 Created: 2009-08-12 Last updated: 2011-11-10Bibliographically approved

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