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  • 1.
    Birgner, Carolina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Pharmaceutical Pharmacology.
    Kindlundh-Högberg, Anna M. S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Biological Research on Drug Dependence.
    Bergström, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Pharmaceutical Pharmacology.
    Altered extracellular levels of DOPAC and HVA in the rat nucleus accumbens shell in response to sub-chronic nandrolone administration and a subsequent amphetamine challenge2007In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 412, no 2, p. 168-172Article in journal (Refereed)
    Abstract [en]

    Associated with acts of violence and polydrug use, abuse of anabolic androgenic steroids (AAS) is an increasing problem in society. The aim of the present study was to elucidate whether sub-chronic treatment with the AAS nandrolone decanoate affects dopamine release and dopamine metabolism in the rat nucleus accumbens shell, before and after an amphetamine challenge. Male Sprague–Dawley rats received daily i.m. injections of nandrolone decanoate (15 mg/kg) or vehicle for 14 days. On day 15, the animals were anaesthetized and a microdialysis probe was implanted into the nucleus accumbens shell. Extracellular fluid was collected 1 h before and 3 h after a single amphetamine injection (5 mg/kg). The samples were then analyzed regarding the content of dopamine, and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), using HPLC with electrochemical detection. Two weeks of nandrolone decanoate administration caused a significant decrease of the basal DOPAC and HVA levels, which remained low during the first hour following the amphetamine challenge. Dopamine levels did not differ significantly between groups, neither after the nandrolone pre-treatment nor the amphetamine challenge. In conclusion, these novel findings indicate that AAS alter the metabolism of dopamine in a brain region involved in the development of drug dependence.

  • 2.
    Jansone, Baiba
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bergstrom, Lena
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Svirskis, Simons
    Lindblom, Jonas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Klusa, Vija
    Wikberg, Jarl E S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Opposite effects of gamma(1)- and gamma(2)-melanocyte stimulating hormone on regulation of the dopaminergic mesolimbic system in rats.2004In: Neurosci Lett, ISSN 0304-3940, Vol. 361, no 1-3, p. 68-71Article in journal (Refereed)
  • 3.
    Kindlundh, Anna MS
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Lindblom, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bergström, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    The anabolic-androgenic steroid nandrolone induces alterations in the density of serotonergic 5HT1B and 5HT2 receptors in the male rat brain2003In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 119, no 1, p. 113-120Article in journal (Refereed)
    Abstract [en]

    Anabolic-androgenic steroids (AAS) are partly misused by males in order to become brave and intoxicated and these agents are highly associated with psychosis, disinhibition, aggression and acts of violence. Since such behavioral states have been related to an imbalanced serotonergic system and the involvement of the serotonergic 5HT(1B) and the 5HT(2) receptors, it was important to discern the impact of AAS on these receptors. The objective of our study was to investigate the effects of 2 weeks of treatment with the AAS nandrolone decanoate at three different doses (1, 5, 15 mg/kg/day) on the total specific binding of the radioligands [(125)I]-(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (5HT(2) receptors) by autoradiography. All doses caused a significant down-regulation of the 5HT(1B) receptor density in the hippocampal CA(1) and in the medial globus pallidus and a significant up-regulation of the 5HT(2) receptor density in the nucleus accumbens shell. Alterations in receptor density were also observed in the lateral globus pallidus, ventromedial hypothalamus, the amygdala and in the intermediate layers of various cortex regions. In conclusion, serotonergic 5HT(1B) or 5HT(2) receptors are likely to play important roles in mediating observed emotional states and behavioral changes among AAS abusers.

  • 4.
    Kindlundh, Anna MS
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Lindblom, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bergström, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Wikberg, Jarl ES
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    The anabolic-androgenic steroid nandrolone decanoate affects the density of dopamine receptors in the male rat brain2001In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 13, no 2, p. 291-296Article in journal (Refereed)
    Abstract [en]

    In recent years a male group of anabolic-androgenic steroid misusers has been identified to share socio-demographic and personality related background factors with misusers of psychotropic substances, as well as being involved in habits of multiple drug use. The present study aimed to assess whether anabolic-androgenic steroids (AAS) would affect the density of the dopamine receptors in areas implicated in reward and behaviour in the male rat brain. The effects of 2 weeks of treatment with i.m. injections of nandrolone decanoate (15 mg/kg/day) on the expression of the D(1)-like and D(2)-like receptors were evaluated by autoradiography. Specific binding of D(1)-like receptors was significantly down regulated in the caudate putamen, the nucleus accumbens core and shell. D(2)-like receptor densities were down regulated in the nucleus accumbens shell, but up regulated in the caudate putamen, the nucleus accumbens core and the ventral tegmental area. These results are compatible with nandrolone induced neuroadaptive alterations in dopamine circuits associated with motor functions and behavioural paradigms known to be affected following AAS misuse.

  • 5.
    Lindblom, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Kindlundh, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bergström, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Wikberg, Jarl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels2003In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 986, no 1-2, p. 139-147Article in journal (Refereed)
    Abstract [en]

    Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.

  • 6.
    Magnusson, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Birgner, Carolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bergström, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hallberg, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nandrolone decanoate administration dose-dependently affects the density of kappa opioid peptide receptors in the rat brain determined by autoradiography2009In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 43, no 2, p. 105-111Article in journal (Refereed)
    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.

  • 7.
    Ploj, Karolina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Roman, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bergstrom, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Effects of neonatal handling on nociceptin/orphanin FQ and opioid peptide levels in female rats2001In: Pharmacology, Biochemistry and Behavior, ISSN 0091-3057, E-ISSN 1873-5177, Vol. 69, no 1-2, p. 173-179Article in journal (Refereed)
    Abstract [en]

    Animals exposed to short periods of handling during the critical period of development, i.e., the first 21 days of life in rats, show attenuated neuroendocrine responses to stress in adult life. We have previously reported long-term changes in brain dynorphin (DYN) peptide levels in male Sprague-Dawley rats after neonatal handling. The purpose of this study was to investigate whether neonatal handling, 15-min individual separation from the mother during postnatal days 1-21, can induce long-term changes in DYNB, Met-enkephalin Arg(6)Phe(7) (MEAP) and nociceptin/orphanin FQ (N/OFQ) immunoreactive (ir) levels in female Sprague-Dawley rats. The peptides were measured in brain and pituitary gland 2 months after the handling procedure. The results reveal that handled (H) rats had increased ir levels of N/OFQ, DYNB and MEAP in the periaqueductal gray (PAG) as compared to nonhandled (NH) controls. Furthermore, H rats had decreased ir levels of DYNB in the frontal cortex and in the amygdala. In contrast to previous findings in male rats, DYNB levels were unaffected in areas related to the hypothalamo - pituitary - adrenal (HPA)-axis. The results indicate that a manipulation early in life can induce persistent neurochemical changes in the N/OFQ and opioid peptide system in female Sprague-Dawley rats.

1 - 7 of 7
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