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  • 1. Adem, Abdu
    et al.
    Madjid, Nather
    Stiedl, Oliver
    Bonito-Oliva, Alessandra
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Holst, Sarah
    Fisone, Gilberto
    Ögren, Sven Ove
    Atypical but not typical antipsychotic drugs ameliorate phencyclidine-induced emotional memory impairments in mice2019In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, no 5, p. 616-628, article id S0924-977X(19)30195-6Article in journal (Refereed)
    Abstract [en]

    Schizophrenia is associated with cognitive impairments related to hypofunction in glutamatergic N-methyl-D-aspartate receptor (NMDAR) transmission. Phencyclidine (PCP), a non-competitive NMDAR antagonist, models schizophrenia-like behavioral symptoms including cognitive deficits in rodents. This study examined the effects of PCP on emotional memory function examined in the passive avoidance (PA) task in mice and the ability of typical and atypical antipsychotic drugs (APDs) to rectify the PCP-mediated impairment. Pre-training administration of PCP (0.5, 1, 2 or 3 mg/kg) dose-dependently interfered with memory consolidation in the PA task. In contrast, PCP was ineffective when administered after training, and immediately before the retention test indicating that NMDAR blockade interferes with memory encoding mechanisms. The typical APD haloperidol and the dopamine D2/3 receptor antagonist raclopride failed to block the PCP-induced PA impairment suggesting a negligible role of D2 receptors in the PCP impairment. In contrast, the memory impairment was blocked by the atypical APDs clozapine and olanzapine in a dose-dependent manner while risperidone was effective only at the highest dose tested (1 mg/kg). The PCP-induced impairment involves 5-HT1A receptor mechanisms since the antagonist NAD-299 blocked the memory impairment caused by PCP and the ability of clozapine to attenuate the impairment by PCP. These results indicate that atypical but not typical APDs can ameliorate NMDAR-mediated memory impairments and support the view that atypical APDs such as clozapine can modulate glutamatergic memory dysfunctions through 5-HT1A receptor mechanisms. These findings suggest that atypical APDs may improve cognitive impairments related to glutamatergic dysfunction relevant for emotional memories in schizophrenia.

  • 2.
    Beltran, D. Campos
    et al.
    Univ Lubeck, Inst Expt & Klin Pharmakol & Toxikol, Lubeck, Germany.
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Quintero, J. E.
    Univ Kentucky, Ctr Microelectrode Technol CenMeT, Lexington, KY 40506 USA;Quanteon LLC, Nicholasville, KY USA.
    Marshall, L.
    Univ Lubeck, Inst Expt & Klin Pharmakol & Toxikol, Lubeck, Germany.
    Amperometric D-serine detecting self-referenced ceramic-based microelectrode arrays2017In: Naunyn-Schmiedeberg's Archives of Pharmacology, ISSN 0028-1298, E-ISSN 1432-1912, Vol. 390, p. S70-S70Article in journal (Other academic)
  • 3.
    Bikovski, Lior
    et al.
    Tel Aviv Univ, Sackler Sch Med, Myers Neurobehav Core Facil, Tel Aviv, Israel.;Netanya Acad Coll, Sch Behav Sci, IL-4223587 Netanya, Israel..
    Robinson, Lianne
    Univ Dundee, Ninewells Hosp, Sch Med, Behav Neurosci Core Facil, Dundee DD1 9SY, Scotland.;Univ Aberdeen, Inst Med Sci, Foresterhill, Aberdeen AB25 2ZD, Scotland..
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Kullander, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Kullander: Formation and Function of Neuronal Circuits.
    Viereckel, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Winberg, Svante
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Winberg: Behavioral Neuroendocrinology.
    Roman, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden..
    Tsoory, Michael
    Weizmann Inst Sci, Dept Vet Resources, Rehovot, Israel..
    Lessons, insights and newly developed tools emerging from behavioral phenotyping core facilities2020In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 334, article id 108597Article, review/survey (Refereed)
    Abstract [en]

    Scientific investigations, in general, and research in neuroscience, in particular, are becoming ever more complex and require the integration of different techniques. Behavioral assays, which are among the most frequently used methodologies in neuroscience, nowadays rely on advanced, sophisticated technologies that require proficient application. Therefore, behavioral core facilities are becoming essential support units, as they provide the specialized expert research services needed to conduct advanced neuroscience. We here review the lessons learned and insights gathered from managing behavioral core facilities in different academic research institutes. This review addresses several issues, including: the advantages of behavioral core facilities, considerations for establishing a behavioral core facility, and the methodological advances made through calibration and standardization of assay protocols and the development of new assays. Collectively, the review highlights the benefits of both working within and collaborating with behavioral core facility units and emphasizes the potential progress in neuro-phenotyping that such facilities provide.

  • 4.
    Campos-Beltran, Diana
    et al.
    Univ Lubeck, Inst Expt & Clin Pharmacol & Toxicol, Ratzeburger Allee 160, D-23562 Lubeck, Germany.
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden.
    Quintero, Jorge E.
    Univ Kentucky, CenMeT, Lexington, KY 40506 USA;Quanteon LLC, Nicholasville, KY 40356 USA.
    Marshall, Lisa
    Univ Lubeck, Inst Expt & Clin Pharmacol & Toxicol, Ratzeburger Allee 160, D-23562 Lubeck, Germany.
    Amperometric Self-Referencing Ceramic Based Microelectrode Arrays for D-Serine Detection2018In: Biosensors, ISSN 2079-6374, Vol. 8, no 1, article id 20Article in journal (Refereed)
    Abstract [en]

    D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a mean sensitivity of 8.61 +/- 0.83 pA/mu M to D-serine, a limit of detection (LOD) of 0.17 +/- 0.01 mu M, and a selectivity ratio of 80:1 or greater for D-serine over ascorbic acid (mean +/- SEM; n = 12) that can be used for freely moving studies.

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  • 5.
    Molinero-Fernandez, Águeda
    et al.
    KTH Royal Inst Technol, Dept Chem, SE-11428 Stockholm, Sweden.;Univ Catolica San Antonio Murcia, UCAM SENS, UCAM HiTech, Murcia 30107, Spain..
    Wang, Qianyu
    KTH Royal Inst Technol, Dept Chem, SE-11428 Stockholm, Sweden..
    Xuan, Xing
    KTH Royal Inst Technol, Dept Chem, SE-11428 Stockholm, Sweden.;Univ Catolica San Antonio Murcia, UCAM SENS, UCAM HiTech, Murcia 30107, Spain..
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Crespo, Gastón A.
    KTH Royal Inst Technol, Dept Chem, SE-11428 Stockholm, Sweden.;Univ Catolica San Antonio Murcia, UCAM SENS, UCAM HiTech, Murcia 30107, Spain..
    Cuartero, Maria
    KTH Royal Inst Technol, Dept Chem, SE-11428 Stockholm, Sweden.;Univ Catolica San Antonio Murcia, UCAM SENS, UCAM HiTech, Murcia 30107, Spain..
    Demonstrating the Analytical Potential of a Wearable Microneedle-Based Device for Intradermal CO2 Detection2024In: ACS Sensors, E-ISSN 2379-3694, Vol. 9, no 1, p. 361-370Article in journal (Refereed)
    Abstract [en]

    Monitoring of carbon dioxide (CO2) body levels is crucial under several clinical conditions (e.g., human intensive care and acid–base disorders). To date, painful and risky arterial blood punctures have been performed to obtain discrete CO2 measurements needed in clinical setups. Although noninvasive alternatives have been proposed to assess CO2, these are currently limited to benchtop devices, requiring trained personnel, being tedious, and providing punctual information, among other disadvantages. To the best of our knowledge, the literature and market lack a wearable device for real-time, on-body monitoring of CO2. Accordingly, we have developed a microneedle (MN)-based sensor array, labeled as CO2–MN, comprising a combination of potentiometric pH- and carbonate (CO32–)-selective electrodes together with the reference electrode. The CO2–MN is built on an epidermal patch that allows it to reach the stratum corneum of the skin, measuring pH and CO32– concentrations directly into the interstitial fluid (ISF). The levels for the pH–CO32– tandem are then used to estimate the PCO2 in the ISF. Assessing the response of each individual MN, we found adequate response time (t95 < 5s), sensitivity (50.4 and −24.6 mV dec–1 for pH and CO32–, respectively), and stability (1.6 mV h–1 for pH and 2.1 mV h–1 for CO32–). We validated the intradermal measurements of CO2 at the ex vivo level, using pieces of rat skin, and then, with in vivo assays in anesthetized rats, showing the suitability of the CO2–MN wearable device for on-body measurements. A good correlation between ISF and blood CO2 concentrations was observed, demonstrating the high potential of the developed MN sensing technology as an alternative to blood-based analysis in the near future. Moreover, these results open new horizons in the noninvasive, real-time monitoring of CO2 as well as other clinically relevant gases.

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  • 6.
    Msghina, Mussie
    et al.
    Örebro Univ, Fac Med & Hlth, Sch Med Sci, Dept Psychiat, Örebro, Narke, Sweden.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Bergerlind, Lise-Lotte
    Kunskapsstod psyk halsa, Expertenheter, Gothenburg, Sweden..
    Schön, Ulla-Karin
    Stockholm Univ, Dept Social Work, Stockholm, Sweden..
    Dahlström, Christian
    Fdn Mental Hlth, Stockholm, Sweden..
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Swedish Schizophren Assoc, Stockholm, Sweden..
    Fundell, Sara
    Swedish Agcy Hlth Technol, Assessment & Assessment Social Serv, Stockholm, Sweden..
    Wallgren, Lena
    Swedish Agcy Hlth Technol, Assessment & Assessment Social Serv, Stockholm, Sweden..
    Tranaeus, Sofia
    Swedish Agcy Hlth Technol, Assessment & Assessment Social Serv, Stockholm, Sweden..
    Höistad, Malin
    Swedish Agcy Hlth Technol, Assessment & Assessment Social Serv, Stockholm, Sweden..
    Prioritised research questions in serious mental illness: a priority setting based on evidence gaps2024In: BMJ Mental Health, E-ISSN 2755-9734, Vol. 27, no 1, p. 1-3, article id e301082Article in journal (Other academic)
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  • 7.
    Schweizer, Nadine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Viereckel, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Smith-Anttila, Casey J. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nordenankar, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Arvidsson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Mahmoudi, Souha
    Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
    Zampera, Andre
    Oramacell, F-75006 Paris, France..
    Jonsson, Hanna Wärner
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Levesque, Daniel
    Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Andersson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Dumas, Sylvie
    Oramacell, F-75006 Paris, France..
    Wallén-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption2016In: eNeuro, E-ISSN 2373-2822, Vol. 3, no 5, article id UNSP e0264Article in journal (Refereed)
    Abstract [en]

    The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson's disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene (Vglut2/Slc17a6) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system.

  • 8.
    Schweizer, Nadine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
    Viereckel, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
    Smith-Anttila, Casey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nordenankar, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Arvidsson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
    Mahmoudi, Souha
    Wärner, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Lévesque, Daniel
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Andersson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Dumas, Sylvie
    Wallén-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Reduced consumption of sugar identifies a regulatory role for a Pitx2/Vglut2 co-expressing subpopulation in the structure and function of the mouse subthalamic nucleusManuscript (preprint) (Other academic)
  • 9.
    Titulaer, Joep
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Björkholm, Carl
    Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden.;Janssen Cilag AB, Solna, Sweden..
    Feltmann, Kristin
    Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Malmlöf, Torun
    Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Mishra, Devesh
    Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Bengtsson Gonzales, Carolina
    Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Schilström, Björn
    Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden..
    The Importance of Ventral Hippocampal Dopamine and Norepinephrine in Recognition Memory2021In: Frontiers in Behavioral Neuroscience, E-ISSN 1662-5153, Vol. 15, article id 667244Article in journal (Refereed)
    Abstract [en]

    Dopaminergic neurons originating from the ventral tegmental area (VTA) and the locus coeruleus are innervating the ventral hippocampus and are thought to play an essential role for efficient cognitive function. Moreover, these VTA projections are hypothesized to be part of a functional loop, in which dopamine regulates memory storage. It is hypothesized that when a novel stimulus is encountered and recognized as novel, increased dopamine activity in the hippocampus induces long-term potentiation and long-term storage of memories. We here demonstrate the importance of increased release of dopamine and norepinephrinein the rat ventral hippocampus on recognition memory, using microdialysis combined to a modified novel object recognition test. We found that presenting rats to a novel object significantly increased dopamine and norepinephrine output in the ventral hippocampus. Two hours after introducing the first object, a second object (either novel or familiar) was placed in the same position as the first object. Presenting the animals to a second novel object significantly increased dopamine and norepinephrine release in the ventral hippocampus, compared to a familiar object. In conclusion, this study suggests that dopamine and norepinephrine output in the ventral hippocampus has a crucial role in recognition memory and signals novelty.

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  • 10.
    Titulaer, Joep
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Dept Physiol & Pharmacol, Sect Neuropsychopharmacol, Stockholm, Sweden..
    Gottfridsson, Rebecca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nordling, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Lund Univ, Div Psychiat, Clin Sci Helsingborg, Lund, Sweden..
    Fagerstrom, Ella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Eberhard, Jonas
    Lund Univ, Div Psychiat, Clin Sci Helsingborg, Lund, Sweden..
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Dept Physiol & Pharmacol, Sect Neuropsychopharmacol, Stockholm, Sweden.;Lund Univ, Div Psychiat, Clin Sci Helsingborg, Lund, Sweden..
    Sex-specific differences and similarities of olanzapine and risperidone on avoidance suppression in rats in the conditioned avoidance response test2023In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1818, article id 148527Article in journal (Refereed)
    Abstract [en]

    It is well known that antipsychotic drugs (APDs) are more effective in reducing symptoms in women than in men, and that women are more sensitive to the side effects of APDs. Therefore, it is of great importance that sex differences in drug responses are considered already in the early stages of drug development. In this study, we investigated whether sex-specific differences could be observed in response to the commonly prescribed APDs olanzapine and risperidone using the conditioned avoidance response (CAR) test. To this end we tested the effect of 1.25 and 2.5 mg/kg olanzapine and 0.25 and 0.4 mg/kg risperidone using female and male Wistar rats in the CAR test. Whereas there were no significant differences between the female and male rats in response to either dose of olanzapine administration, an injection of 0.4 mg/kg risperidone significantly suppressed avoidance more in female rats than in male rats. In addition, we found that the estrous cycle of the female rats did not have a significant effect on the avoidance response. In conclusion, we show that there are sex-specific differences as well as similarities between female and male rats in the CAR test and novel APDs should be tested on female and male rats in the future.

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  • 11.
    Titulaer, Joep
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Dept Physiol & Pharmacol, Sect Neuropsychopharmacol, Stockholm, Sweden.;Biomed Ctr, Husargatan3,, Uppsala 75123, Sweden..
    Radhe, Ottil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mazrina, Jasmine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Ström, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Svensson, Torgny H.
    Karolinska Inst, Dept Physiol & Pharmacol, Sect Neuropsychopharmacol, Stockholm, Sweden..
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Dept Physiol & Pharmacol, Sect Neuropsychopharmacol, Stockholm, Sweden..
    Sodium nitroprusside enhances the antipsychotic-like effect of olanzapine but not clozapine in the conditioned avoidance response test in rats2022In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 60, p. 48-54Article in journal (Refereed)
    Abstract [en]

    The nitric oxide (NO)-donor, sodium nitroprusside (SNP) has been proposed as an adjunct treatment to enhance the effect of antipsychotic drugs (APDs). As NO constitutes an important downstream signaling molecule of N-methyl-D-aspartate receptors, SNP may alleviate symptoms of schizophrenia by modulating glutamatergic signaling. We previously showed that SNP enhances the antipsychotic-like effect of a sub-effective dose of risperidone in the conditioned avoidance response (CAR) test, indicating that adjunct SNP may be used to lower the dose of risperidone and in this way reduce the risk of side effects. By using the CAR test, we here investigated if SNP also enhances the antipsychotic-like effect of olanzapine or clozapine. Importantly, SNP (1.5 mg/kg) significantly enhanced the antipsychotic-like effect of olanzapine (1.25 and 2.5mg/kg) to a clinically relevant level, supporting the potential clinical use of SNP as an adjunct treatment to improve the effect of APDs. However, SNP (1.5 mg/kg) did not increase the antipsychotic-like effect of clozapine (5 and 6 mg/kg). Moreover, we found that the rats developed tolerance towards clozapine after repeated administrations. Thus, our study motivates further investigation using different preclinical models to assess the effect of adjunct treatment of SNP to APDs, also targeting the negative symptoms and cognitive deficits seen in schizophrenia.

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  • 12.
    Viereckel, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Wallén-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    A Physiological Insight into Real-Time Glutamate Release upon Optogenetic Stimulation in vivo 2017Manuscript (preprint) (Other academic)
  • 13.
    Viereckel, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Wallén-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Validated multi‐step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus2018In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 145, no 2, p. 125-138Article in journal (Refereed)
    Abstract [en]

    Precise quantification of extracellular glutamate concentrations upon neuronal activation is crucial for the understanding of brain function and neurological disorders. While optogenetics is an outstanding method for the correlation between distinct neurons and their role in circuitry and behavior, the electrochemically inactive nature of glutamate has proven challenging for recording upon optogenetic stimulations. This difficulty is due to the necessity for using enzyme-coated microelectrodes and the risk for light-induced artifacts. In this study, we establish a method for the combination of invivo optogenetic stimulation with selective measurement of glutamate concentrations using enzyme-coated multielectrode arrays and amperometry. The glutamatergic subthalamic nucleus (STN), which is the main electrode target site in deep brain stimulation treatment of advanced Parkinsons disease, has recently proven opotogenetically targetable in Pitx2-Cre-transgenic mice and was here used as model system. Upon stereotactic injection of viral Channelrhodopsin2-eYFP constructs into the STN, amperometric recordings were performed at a range of optogenetic stimulation frequencies in the globus pallidus, the main STN target area, in anesthetized mice. Accurate quantification was enabled through a multi-step analysis approach based on self-referencing microelectrodes and repetition of the experimental protocol at two holding potentials, which allowed for the identification, isolation and removal of photoelectric and photoelectrochemical artifacts. This study advances the field of invivo glutamate detection with combined optogenetics and amperometric recordings by providing a validated analysis framework for application in a wide variety of glutamate-based approaches in neuroscience.

  • 14.
    Wang, Dong V.
    et al.
    NIDA, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA..
    Viereckel, Thomas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
    Zell, Vivien
    Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA..
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Broker, Carl J.
    NIDA, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA..
    Talishinsky, Aleksandr
    NIDA, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA..
    Yoo, Ji Hoon
    Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA..
    Galinato, Melissa H.
    Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA..
    Arvidsson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Kesner, Andrew J.
    Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA..
    Hnasko, Thomas S.
    Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA..
    Wallén-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Ikemoto, Satoshi
    NIDA, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA..
    Disrupting Glutamate Co-transmission Does Not Affect Acquisition of Conditioned Behavior Reinforced by Dopamine Neuron Activation2017In: Cell Reports, E-ISSN 2211-1247, Vol. 18, no 11, p. 2584-2591Article in journal (Refereed)
    Abstract [en]

    Dopamine neurons in the ventral tegmental area (VTA) were previously found to express vesicular glutamate transporter 2 (VGLUT2) and to co-transmit glutamate in the ventral striatum (VStr). This capacity may play an important role in reinforcement learning. Although it is known that activation of the VTA-VStr dopamine system readily reinforces behavior, little is known about the role of glutamate co-transmission in such reinforcement. By combining electrode recording and optogenetics, we found that stimulation of VTA dopamine neurons in vivo evoked fast excitatory responses in many VStr neurons of adult mice. Whereas conditional knockout of the gene encoding VGLUT2 in dopamine neurons largely eliminated fast excitatory responses, it had little effect on the acquisition of conditioned responses reinforced by dopamine neuron activation. Therefore, glutamate co-transmission appears dispensable for acquisition of conditioned responding reinforced by DA neuron activation.

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  • 15.
    Wang, Qianyu
    et al.
    KTH Royal Inst Technol, Sch Engn Sci Chem, Dept Chem, Biotechnol & Hlth, S-10044 Stockholm, Sweden..
    Molinero-Fernandez, Agueda
    KTH Royal Inst Technol, Sch Engn Sci Chem, Dept Chem, Biotechnol & Hlth, S-10044 Stockholm, Sweden..
    Casanova, Ana
    KTH Royal Inst Technol, Sch Engn Sci Chem, Dept Chem, Biotechnol & Hlth, S-10044 Stockholm, Sweden..
    Titulaer, Joep
    Campillo-Brocal, Jonatan C.
    Univ Murcia, Campus Univ Espinardo, Dept Genet & Microbiol, Murcia 30100, Spain..
    Konradsson-Geuken, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Crespo, Gaston A.
    KTH Royal Inst Technol, Sch Engn Sci Chem, Dept Chem, Biotechnol & Hlth, S-10044 Stockholm, Sweden..
    Cuartero, Maria
    KTH Royal Inst Technol, Sch Engn Sci Chem, Dept Chem, Biotechnol & Hlth, S-10044 Stockholm, Sweden..
    Intradermal Glycine Detection with a Wearable Microneedle Biosensor: The First In Vivo Assay2022In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 94, no 34, p. 11856-11864Article in journal (Refereed)
    Abstract [en]

    Glycine (GLY) is gaining importance in medical diagnoses due to its relationship with multiple physiological functions. Today, GLY is exclusively analyzed using instrumentation centralized in clinical labs, and a tangible point-of-care tool that gathers real-time data from the patient for effective and fast evaluations is lacking. Relevant clinical advances are expected as soon as the rapid provision of both punctual and continuous measurements is possible. In that context, this work presents a microneedle (MN)-based biosensor for intradermal GLY detection in interstitial fluid (ISF). The MN tip is externally tailored to detect GLY levels through the hydrogen peroxide formed in its reaction with a quinoprotein-based GLY oxidase enzyme. The analytical performance of the MN biosensor indicates a fast response time (< 7 s); acceptable reversibility, reproducibility, and stability; as well as a wide linear range of response (25-600 mu M) that covers the physiological levels of GLY in ISF. The MN biosensor conveniently exhibits high selectivity for GLY over other compounds commonly found in ISF, and the response is not influenced by temperature, pH, or skin insertions. Validated intradermal measurements of GLY were obtained at the in vitro (with pieces of rat skin), ex vivo (on-body tests of euthanized rats) and in vivo (on-body tests of anesthetized rats) levels, demonstrating its ability to produce accurate physiological data. The developed GLY MN biosensor is skin-wearable and provides reliable, real-time intradermal GLY measurements in ISF by means of a minimally invasive approach.

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