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  • 1. Barlow, Rebecca L.
    et al.
    Alsiö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Jupp, Bianca
    Rabinovich, Rebecca
    Shrestha, Saurav
    Roberts, Angela C.
    Robbins, Trevor W.
    Dalley, Jeffrey W.
    Markers of Serotonergic Function in the Orbitofrontal Cortex and Dorsal Raphe Nucleus Predict Individual Variation in Spatial-Discrimination Serial Reversal Learning2015In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 40, no 7, p. 1619-1630Article in journal (Refereed)
    Abstract [en]

    Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies. Impaired flexibility also results from interventions that alter serotonin (5-HT) and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS). However, it is unclear whether similar mechanisms underpin naturally occurring variations in behavioral flexibility. In the present study, we used a spatial-discrimination serial reversal procedure to investigate interindividual variability in behavioral flexibility in rats. We show that flexibility on this task is improved following systemic administration of the 5-HT reuptake inhibitor citalopram and by low doses of the DA reuptake inhibitor GBR12909. Rats in the upper quintile of the distribution of perseverative responses during repeated S-R reversals showed significantly reduced levels of the 5-HT metabolite, 5-hydroxy-indoleacetic acid, in the OFC. Additionally, 5-HT2A receptor binding in the OFC of mid-and high-quintile rats was significantly reduced compared with rats in the low-quintile group. These perturbations were accompanied by an increase in the expression of monoamine oxidase-A (MAO-A) and MAO-B in the lateral OFC and by a decrease in the expression of MAO-A, MAO-B, and tryptophan hydroxylase in the dorsal raphe nucleus of highly perseverative rats. We found no evidence of significant differences in markers of DA and 5-HT function in the DMS or MAO expression in the ventral tegmental area of low-vs high-perseverative rats. These findings indicate that diminished serotonergic tone in the OFC may be an endophenotype that predisposes to behavioral inflexibility and other forms of compulsive behavior.

  • 2.
    Browning, Michael
    et al.
    Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England.
    Grol, Maud
    Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England.
    Ly, Verena
    Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England.
    Goodwin, Guy M.
    Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England.
    Holmes, Emily A.
    Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England.
    Harmer, Catherine J.
    Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England.
    Using an Experimental Medicine Model to Explore Combination Effects of Pharmacological and Cognitive Interventions for Depression and Anxiety2011In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 36, no 13, p. 2689-2697Article in journal (Refereed)
    Abstract [en]

    Selective serotonergic reuptake inhibitors (SSRIs) and cognitive therapies are effective in the treatment of anxiety and depression. Previous research suggests that both forms of treatments may work by altering cognitive biases in the processing of affective information. The current study assessed the effects of combining an SSRI with a cognitive intervention on measures of affective processing bias and resilience to external challenge. A total of 62 healthy participants were randomly assigned to receive either 7 days of citalopram (20 mg) or placebo capsules while also completing either an active or a control version of a computerized cognitive bias training task. After treatment, standard measures of affective processing bias were collected. Participants' resilience to external stress was also tested by measuring the increase in negative symptoms induced by a negative mood induction. Participants who received both citalopram and the active cognitive bias training task showed a smaller alteration in emotional memory and categorization bias than did those who received either active intervention singly. The degree to which memory for negative information was altered by citalopram predicted participants' resistance to the negative mood induction. These results suggest that co-administration of an SSRI and a cognitive training intervention can reduce the effectiveness of either treatment alone in terms of anxiety-and depression-relevant emotional processing. More generally, the findings suggest that pinpointing the cognitive actions of treatments may inform future development of combination strategies in mental health. Neuropsychopharmacology (2011) 36, 2689-2697; doi: 10.1038/npp.2011.159; published online 10 August 2011

  • 3. Cassataro, Daniela
    et al.
    Bergfeldt, Daniella
    Malekian, Cariz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Van Snellenberg, Jared X.
    Thanos, Panayotis K.
    Fishell, Gord
    Sjulson, Lucas
    Reverse Pharmacogenetic Modulation of the Nucleus Accumbens Reduces Ethanol Consumption in a Limited Access Paradigm2014In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 39, no 2, p. 283-290Article in journal (Refereed)
    Abstract [en]

    Bilateral stereotactic lesioning of the nucleus accumbens (NAc) core reduces relapse rates in alcohol-dependent patients but may cause irreversible cognitive deficits. Deep brain stimulation has similar effects but requires costly implanted hardware and regular surgical maintenance. Therefore, there is considerable interest in refining these approaches to develop reversible, minimally invasive treatments for alcohol dependence. Toward this end, we evaluated the feasibility of a reverse pharmacogenetic approach in a preclinical mouse model. We first assessed the predictive validity of a limited access ethanol consumption paradigm by confirming that electrolytic lesions of the NAc core decreased ethanol consumption, recapitulating the effects of similar lesions in humans. We then used this paradigm to test the effect of modulating activity in the NAc using the Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) hM3Dq and hM4Di. We found that increasing activity with hM3Dq had no effect, but suppressing activity with hM4Di reduced alcohol consumption to a similar extent as lesioning without affecting consumption of water or sucrose. These results may represent early steps toward a novel neurosurgical treatment modality for alcohol dependence that is reversible and externally titratable, yet highly targetable and less invasive than current approaches such as lesioning or deep brain stimulation.

  • 4.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 555-563Article in journal (Refereed)
    Abstract [en]

    The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

  • 5.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
    Linnman, Clas
    P.A.I.N. Group, Department of Anesthesia, Children's Hospital, Boston, MA, USA.
    Pissiota, Anna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bani, Massimo
    GlaxoSmithKline, Medicine Centre, Verona, Italy.
    Bettica, Paolo
    GlaxoSmithKline, Medicine Centre, Verona, Italy.
    M Pich, Emilio
    GlaxoSmithKline, Medicine Centre, Verona, Italy.
    Jacobsson, Eva
    Uppsala University Hospital and Quintiles AB Phase I Services, Uppsala, Sweden.
    Wahlsted, Kurt
    Uppsala University Hospital and Quintiles AB Phase I Services, Uppsala, Sweden.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder2012In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 37, no 10, p. 2222-2232Article in journal (Refereed)
    Abstract [en]

    The amygdala is a key structure in the pathophysiology of anxiety disorders, and a putative target for anxiolytic treatments, Selective serotonin reuptake inhibitors (SSRIs) and placebo seem to induce anxiolytic effects by attenuating amygdala responsiveness. However, conflicting amygdala findings have also been reported. Moreover, the neural profile of responders and nonresponders is insufficiently characterized and it remains unknown whether SSRIs and placebo engage common or distinct amygdala subregions or different modulatory cortical areas. We examined similarities and differences in the neural response to SSRIs and placebo in patients with social anxiety disorder (SAD). Positron emission tomography (PET) with oxygen-15-labeled water was used to assess regional cerebral blood flow (rCBF) in 72 patients with SAD during an anxiogenic public speaking task, before and after 6-8 weeks of treatment under double-blind conditions. Response rate was determined by the Clinical Global Impression-Improvement scale. Conjunction analysis revealed a common rCBF-attenuation from pre- to post-treatment in responders to SSRIs and placebo in the left basomedial/basolateral and right ventrolateral amygdala. This rCBF pattern con-elated with behavioral measures of reduced anxiety and differentiated responders from nonresponders. However, nonanxiolytic treatment effects were also observed in the amygdala. All subgroups, including nonresponders, showed deactivation of the left lateral part of the amygdala. No rCBF differences were found between SSRI responders and placebo responders. This study provides new insights into the brain dynamics underlying anxiety relief by demonstrating common amygdala targets for pharmacologically and psychologically induced anxiety reduction, and by showing that the amygdala is functionally heterogeneous in anxiolysis.

  • 6. Feld, Gordon B
    et al.
    Wilhem, Ines
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rüdel, Benjamin
    Klameth, Corinna
    Born, Jan
    Hallschmid, Manfred
    Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation2016In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 41, no 6, p. 1540-1550Article in journal (Refereed)
    Abstract [en]

    The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters and memory consolidation in 16 men and 16 women (aged 18-30 years), who learned a declarative word-pair task and a procedural finger sequence tapping task in the evening before intranasal insulin (160 IU) or placebo administration and 8 h of nocturnal sleep. On the subsequent evening, they learned interfering word-pairs and a new finger sequence before retrieving the original memories. Insulin increased growth hormone concentrations in the first night-half and EEG delta power during the second 90 min of non-rapid-eye-movement sleep. Insulin treatment impaired the acquisition of new contents in both the declarative and procedural memory systems on the next day, whereas retrieval of original memories was unchanged. Results indicate that sleep-associated memory consolidation is not a primary mediator of insulin's acute memory-improving effect, but that the peptide acts on mechanisms that diminish the subsequent encoding of novel information. Thus, by inhibiting processes of active forgetting during sleep, central nervous insulin might reduce the interfering influence of encoding new information.

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  • 7.
    Feltmann, Kristin
    et al.
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden..
    Giuliano, Chiara
    Univ Cambridge, Dept Psychol, Cambridge, England.;Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England..
    Everitt, Barry J.
    Univ Cambridge, Dept Psychol, Cambridge, England.;Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England..
    Steensland, Pia
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden..
    Alsiö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Univ Cambridge, Dept Psychol, Cambridge, England.; Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England..
    The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 617-626Article in journal (Refereed)
    Abstract [en]

    Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats. OSU6162 significantly reduced binge-like intake of chocolate-flavored sucrose pellets without affecting prior chow intake. Furthermore, OSU6162 significantly reduced the cue-controlled seeking of chocolate-flavored sucrose pellets under a second-order schedule of reinforcement before, but not after, the delivery and ingestion of reward, indicating a selective effect on incentive motivational processes. In contrast, the dopamine D2/D3 receptor antagonist raclopride reduced the seeking of chocolate-flavored sucrose pellets both pre-and post reward ingestion and also reduced responding under simpler schedules of seeking behavior. The D1/5 receptor antagonist SCH23390 had no effect on instrumental behavior under any reinforcement schedule tested. Finally, local administration of OSU6162 into the nucleus accumbens core, but not dorsolateral striatum, selectively reduced cue-controlled sucrose seeking. In conclusion, the present results show that OSU6162 reduces binge-like eating behavior and attenuates the impact of cues on seeking of palatable food. This indicates that OSU6162 might serve as a novel BED medication.

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  • 8. Hensch, Tilman
    et al.
    Wargelius, Hanna-Linn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Herold, Ulf
    Lesch, Klaus-Peter
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Brocke, Burkhard
    Further evidence for an association of 5-HTTLPR with intensity dependence of auditory-evoked potentials2006In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 31, no 9, p. 2047-2054Article in journal (Refereed)
    Abstract [en]

    Intensity dependence of auditory-evoked potentials (IAEP) has been suggested as an indicator of central serotonergic neurotransmission. Two recent studies investigated a possible association of IAEP with a functional polymorphism in the transcriptional control region of the serotonin transporter gene (5-HTTLPR) that has a short (s) and a long (l) variant. Although both studies found an association between 5-HTTLPR and IAEP, Gallinat et al found l/l individuals to exhibit lower IAEP, whereas Strobel et al observed stronger IAEP in l/l individuals. These conflicting results require further evaluation and more attention needs to be paid to variables that are known to be confounded with the effects of IAEP and 5-HTTLPR. Using a paradigm comparable to Strobel et al, the present study analyzes the effect of 5-HTTLPR on IAEP in a healthy male student sample (N=91; age=23 years, SD=1.9) that was homogenous for most significant confounding variables. A stronger IAEP was shown in l/l individuals, irrespective of the method of IAEP parametrization. This also held at retest after 3 weeks in a subsample (N=18). Given the successful replication of Strobel et al, several possible reasons for conflicting results with regard to Gallinat et al are discussed. It is argued that the most significant difference between Gallinat et al on the one hand, and Strobel et al and this study on the other, is that different intensity ranges are used which impact IAEP. Therefore, this study encourages further analysis of dose dependence of results.

  • 9.
    Kask, Kristiina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gulinello, Maria
    Bäckström, Torbjörn
    Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
    Geyer, Mark A
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Patients with premenstrual dysphoric disorder have increased startle response across both cycle phases and lower levels of prepulse inhibition during the late luteal phase of the menstrual cycle2008In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 33, no 9, p. 2283-2290Article in journal (Refereed)
    Abstract [en]

    Patients with premenstrual dysphoric disorder (PMDD) experience their most intense symptoms during the late luteal phase. The aim of the current study was to compare acoustic startle response and prepulse inhibition in PMDD patients and controls during the follicular and late luteal phases of the menstrual cycle. Following two months of prospective daily ratings on the Cyclicity Diagnoser scale, 30 PMDD patients and 30 asymptomatic controls, between the ages of 20 and 46, were included in the study. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of m. orbicularis oculi. Twenty pulse-alone trials (115 dB 40 ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115 dB 40 ms noise burst preceded at a 100 ms interval by 20 ms prepulses that were 72, 74, 78, or 86 dB. PMDD patients had a significantly higher startle response than controls during both phases of the menstrual cycle (p<0.05). PMDD patients exhibited lower levels of prepulse inhibition with 78 dB and 86 dB prepulses compared to control subjects in the luteal (p<0.01) but not in the follicular phase. Whereas control subjects displayed increased PPI during the late luteal phase compared to the follicular phase (p<0.01), PPI magnitude remained unchanged in PMDD patients between cycle phases. Relative to controls, PMDD patients displayed increased startle reactivity across both menstrual cycle phases and deficits in prepulse inhibition of acoustic startle during the late luteal phase. These findings are consistent with an altered response to ovarian steroids among PMDD patients.

  • 10.
    Kuzmin, Alexander
    et al.
    Department of Clinical Neuroscience, Division of Drug Dependence Research, Karolinska Institutet, Stockholm, Sweden.
    Kreek, Mary Jeanne
    Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
    Bakalkin, Georgy
    Department of Clinical Neuroscience, Division of Drug Dependence Research, Karolinska Institutet, Stockholm, Sweden.
    Liljequist, Sture
    Department of Clinical Neuroscience, Division of Drug Dependence Research, Karolinska Institutet, Stockholm, Sweden.
    The nociceptin/orphanin FQ receptor agonist Ro 64-6198 reduces alcohol self-administration and prevents relapse-like alcohol drinking2007In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 32, no 4, p. 902-10Article in journal (Refereed)
    Abstract [en]

    Effects of the opioid receptor like-1 (ORL-1) receptor agonist Ro 64-6198 (0.1, 0.3, and 1.0 mg/kg intraperitoneally (i.p.)) on operant ethanol self-administration and activation of self-administration by ethanol deprivation were studied in male Wistar rats. Acute administration of Ro 64-6198 caused a dose-dependent reduction of ethanol self-administration. In comparison, the opioid antagonist naltrexone (0.1, 0.3, and 1.0 mg/kg i.p.) inhibited ethanol self-administration at all doses tested. Ethanol deprivation for 10 days significantly increased ethanol self-administration during the first 2 days after deprivation. Daily pretreatment with Ro 64-6198 (0.3 mg/kg) or naltrexone (0.3 mg/kg) during the last 3 days of ethanol deprivation abolished the deprivation-induced increase in ethanol intake. Thus, stimulation of the ORL-1 receptors by Ro 64-6198 reduced the acute reinforcing effects of ethanol and prevented relapse-like behavior in the ethanol-deprivation model in a similar manner as a blockade of opioid receptors by naltrexone. Ro 64-6198 at 0.1 and 0.3 mg/kg doses did not alter self-administration of 0.2% saccharin solution, indicating an apparent selectivity of this compound in modification of ethanol reward. These findings add further support to the idea that Ro 64-6198 and potentially other synthetic ORL-1 receptor agonists are as effective as naltrexone in blocking the actions of ethanol important for its addictive potential in animal experiments, and therefore may have therapeutic value in the treatment of alcoholism.

  • 11.
    Shariatgorji, Mohammadreza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Svenningsson, Per
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mass Spectrometry Imaging, an Emerging Technology in Neuropsychopharmacology2014In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 39, no 1, p. 34-49Article, review/survey (Refereed)
    Abstract [en]

    Mass spectrometry imaging is a powerful tool for directly determining the distribution of proteins, peptides, lipids, neurotransmitters, metabolites and drugs in neural tissue sections in situ. Molecule-specific imaging can be achieved using various ionization techniques that are suited to different applications but which all yield data with high mass accuracies and spatial resolutions. The ability to simultaneously obtain images showing the distributions of chemical species ranging from metal ions to macromolecules makes it possible to explore the chemical organization of a sample and to correlate the results obtained with specific anatomical features. The imaging of biomolecules has provided new insights into multiple neurological diseases, including Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used in conjunction with other imaging techniques in order to identify correlations between changes in the distribution of important chemical species and other changes in the properties of the tissue. Here we review the applications of mass spectrometry imaging in neuroscience research and discuss its potential. The results presented demonstrate that mass spectrometry imaging is a useful experimental method with diverse applications in neuroscience.

  • 12.
    Sjöberg, Rickard L
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Ducci, Francesca
    Barr, Christina S
    Newman, Timothy K
    Dell'osso, Liliana
    Virkkunen, Matti
    Goldman, David
    A Non-Additive Interaction of a Functional MAO-A VNTR and Testosterone Predicts Antisocial Behavior.2008In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 33, no 2, p. 425-420Article in journal (Refereed)
    Abstract [en]

    A functional VNTR polymorphism in the promoter of the monoamine oxidase A gene (MAOA-LPR) has previously been shown to be an important predictor of antisocial behavior in men. Testosterone analogues are known to interact with the MAOA promoter in vitro to influence gene transcription as well as in vivo to influence CSF levels of the MAO metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in human males. We examined the possible joint effects of testosterone (measured in CSF) and MAOA-LPR genotype on antisocial personality disorder and scores on the Brown-Goodwin Aggression scale in 95 unrelated male criminal alcoholics and 45 controls. The results confirm that MAOA genotype and CSF testosterone interact to predict antisocial behaviors. The MAOA/testosterone interaction also predicted low levels of CSF MHPG, which tentatively suggests the possibility that the interaction may be mediated by a direct effect on gene transcription. If replicated these findings offer plausible explanations for previous inconsistencies in studies of the relationship between testosterone and male human aggression, as well as for how MAOA genotype may influence aggressive behavior in human males.

  • 13.
    Todkar, Aniruddha
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Vrettou, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Boon, Wout
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Bendre, Megha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Tuvblad, Catherine
    Örebro University, School of Law, Psychology and Social Work.
    Andershed, Henrik
    Örebro University, School of Law, Psychology and Social Work.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Fkbp5/FKBP5 mediates the influence of parent-offspring relationship on alcohol drinking in young adult rats and humansIn: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634XArticle in journal (Other academic)
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