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  1. Article: Effects of the anticonvulsant lacosamide compared to valproate and lamotrigine on cocaine-enhanced reward in rats

    Béguin, Cécile / Potter, David N / Carlezon, William A., Jr / Stöhr, Thomas / Cohen, Bruce M

    Brain research. 2012 Oct. 15, v. 1479

    2012  

    Abstract: Some drugs developed as anticonvulsants (notably, valproate and lamotrigine) have therapeutic effects in bipolar and related disorders. Lacosamide, a recently approved anticonvulsant, has unique effects on sodium channels that may play a role in ... ...

    Abstract Some drugs developed as anticonvulsants (notably, valproate and lamotrigine) have therapeutic effects in bipolar and related disorders. Lacosamide, a recently approved anticonvulsant, has unique effects on sodium channels that may play a role in producing the mood-stabilizing effects of anticonvulsant drugs. We tested whether lacosamide would have effects similar to or different from valproate and lamotrigine in a model of reward and elevated mood. The intracranial self-stimulation (ICSS) test is sensitive to the function of brain reward systems. Changes in ICSS may model aspects of disorders characterized by abnormalities of reward and motivation. Cocaine elevates mood, and reduction of cocaine-induced facilitation of ICSS has been used to predict antimanic-like or mood stabilizing effects of drugs. We tested lacosamide, lamotrigine, and valproate in the rat ICSS test alone or in the presence of cocaine. A high dose of lacosamide (30mg/kg) significantly elevated ICSS thresholds, indicating that it reduced the rewarding impact of medial forebrain bundle stimulation. Lower doses (3–10mg/kg) did not alter ICSS, but blocked the cocaine-induced lowering of ICSS thresholds. The highest doses of valproate (300mg/kg) and lamotrigine (30mg/kg) also elevated ICSS thresholds, and only these high doses significantly lowered cocaine-induced effects. Of the drugs tested, only lacosamide significantly attenuated the reward-facilitating effects of cocaine at doses that had no effects on ICSS response in the absence of cocaine. Abnormalities of mood and reward are common in psychiatric disorders, and these results suggest that lacosamide deserves further study in models of these disorders.
    Keywords anticonvulsants ; brain ; cocaine ; emotions ; models ; motivation ; rats ; sodium channels ; therapeutics
    Language English
    Dates of publication 2012-1015
    Size p. 44-51.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2012.08.030
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 88/503: Show issues

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  2. Article: Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues

    Béguin, Cécile / Potuzak, Justin / Xu, Wei / Liu-Chen, Lee-Yuan / Streicher, John M / Groer, Chad E / Bohn, Laura M / Carlezon, William A., Jr / Cohen, Bruce M

    Bioorganic & medicinal chemistry letters. 2012 Jan. 15, v. 22, no. 2

    2012  

    Abstract: The kappa opioid receptor (KOPR) has been identified as a potential drug target to prevent or alter the course of mood, anxiety and addictive disorders or reduce response to stress. In a search for highly potent and selective KOPR partial agonists as ... ...

    Abstract The kappa opioid receptor (KOPR) has been identified as a potential drug target to prevent or alter the course of mood, anxiety and addictive disorders or reduce response to stress. In a search for highly potent and selective KOPR partial agonists as pharmacological tools, we have modified 12-epi-salvinorin A, a compound which we have previously observed to be a KOPR partial agonist. Five analogues of 12-epi-salvinorin A were synthesized and their effects on G protein activation as well as β-arrestin2 recruitment were evaluated. Only 12-epi-salvinorin A (1) partially activated signaling through G proteins, yet acted as a full agonist in the β-arrestin 2 DiscoveRx assay. Other salvinorin analogues tested in these functional assays were full agonists in both assays of KOPR activation. By comparison, the non-selective opioid ligand nalbuphine, known to be a partial agonist for G-protein activation, was also a partial agonist for the β-arrestin mediated signaling pathway activated through KOPR.
    Keywords proteins ; drugs ; stress response ; signal transduction ; agonists ; anxiety
    Language English
    Dates of publication 2012-0115
    Size p. 1023-1026.
    Publishing place Elsevier Ltd
    Document type Article
    Note 2019-12-06
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2011.11.128
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3203: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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  3. Article: Mania-like behavior induced by disruption of CLOCK

    Roybal, Kole / Theobold, David / Graham, Ami / DiNieri, Jennifer A / Russo, Scott J / Krishnan, Vaishnav / Chakravarty, Sumana / Peevey, Joseph / Oehrlein, Nathan / Birnbaum, Shari / Vitaterna, Martha H / Orsulak, Paul / Takahashi, Joseph S / Nestler, Eric J / Carlezon, William A. Jr / McClung, Colleen A

    Proceedings of the National Academy of Sciences of the United States of America. 2007 Apr. 10, v. 104, no. 15

    2007  

    Abstract: Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly ... ...

    Abstract Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of this disorder remains unclear. Here we show that mice carrying a mutation in the Clock gene display an overall behavioral profile that is strikingly similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, lower anxiety, and an increase in the reward value for cocaine, sucrose, and medial forebrain bundle stimulation. Chronic administration of the mood stabilizer lithium returns many of these behavioral responses to wild-type levels. In addition, the Clock mutant mice have an increase in dopaminergic activity in the ventral tegmental area, and their behavioral abnormalities are rescued by expressing a functional CLOCK protein via viral-mediated gene transfer specifically in the ventral tegmental area. These findings establish the Clock mutant mice as a previously unrecognized model of human mania and reveal an important role for CLOCK in the dopaminergic system in regulating behavior and mood.
    Language English
    Dates of publication 2007-0410
    Size p. 6406-6411.
    Publishing place National Academy of Sciences
    Document type Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

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  4. Article: Effects of the anticonvulsant lacosamide compared to valproate and lamotrigine on cocaine-enhanced reward in rats

    Béguin, Cécile / Potter, David N. / Carlezon, William A., Jr / Stöhr, Thomas / Cohen, Bruce M.

    Brain research

    Volume v. 1479

    Abstract: Some drugs developed as anticonvulsants (notably, valproate and lamotrigine) have therapeutic effects in bipolar and related disorders. Lacosamide, a recently approved anticonvulsant, has unique effects on sodium channels that may play a role in ... ...

    Abstract Some drugs developed as anticonvulsants (notably, valproate and lamotrigine) have therapeutic effects in bipolar and related disorders. Lacosamide, a recently approved anticonvulsant, has unique effects on sodium channels that may play a role in producing the mood-stabilizing effects of anticonvulsant drugs. We tested whether lacosamide would have effects similar to or different from valproate and lamotrigine in a model of reward and elevated mood. The intracranial self-stimulation (ICSS) test is sensitive to the function of brain reward systems. Changes in ICSS may model aspects of disorders characterized by abnormalities of reward and motivation. Cocaine elevates mood, and reduction of cocaine-induced facilitation of ICSS has been used to predict antimanic-like or mood stabilizing effects of drugs. We tested lacosamide, lamotrigine, and valproate in the rat ICSS test alone or in the presence of cocaine. A high dose of lacosamide (30mg/kg) significantly elevated ICSS thresholds, indicating that it reduced the rewarding impact of medial forebrain bundle stimulation. Lower doses (3–10mg/kg) did not alter ICSS, but blocked the cocaine-induced lowering of ICSS thresholds. The highest doses of valproate (300mg/kg) and lamotrigine (30mg/kg) also elevated ICSS thresholds, and only these high doses significantly lowered cocaine-induced effects. Of the drugs tested, only lacosamide significantly attenuated the reward-facilitating effects of cocaine at doses that had no effects on ICSS response in the absence of cocaine. Abnormalities of mood and reward are common in psychiatric disorders, and these results suggest that lacosamide deserves further study in models of these disorders.
    Keywords sodium channels ; models ; therapeutics ; anticonvulsants ; cocaine ; emotions ; motivation ; rats ; brain
    Language English
    Document type Article
    ISSN 0006-8993
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article: Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues

    Béguin, Cécile / Potuzak, Justin / Xu, Wei / Liu-Chen, Lee-Yuan / Streicher, John M. / Groer, Chad E. / Bohn, Laura M. / Carlezon, William A., Jr. / Cohen, Bruce M.

    Bioorganic & medicinal chemistry letters

    Volume v. 22,, Issue no. 2

    Abstract: The kappa opioid receptor (KOPR) has been identified as a potential drug target to prevent or alter the course of mood, anxiety and addictive disorders or reduce response to stress. In a search for highly potent and selective KOPR partial agonists as ... ...

    Abstract The kappa opioid receptor (KOPR) has been identified as a potential drug target to prevent or alter the course of mood, anxiety and addictive disorders or reduce response to stress. In a search for highly potent and selective KOPR partial agonists as pharmacological tools, we have modified 12-epi-salvinorin A, a compound which we have previously observed to be a KOPR partial agonist. Five analogues of 12-epi-salvinorin A were synthesized and their effects on G protein activation as well as β-arrestin2 recruitment were evaluated. Only 12-epi-salvinorin A (1) partially activated signaling through G proteins, yet acted as a full agonist in the β-arrestin 2 DiscoveRx assay. Other salvinorin analogues tested in these functional assays were full agonists in both assays of KOPR activation. By comparison, the non-selective opioid ligand nalbuphine, known to be a partial agonist for G-protein activation, was also a partial agonist for the β-arrestin mediated signaling pathway activated through KOPR.
    Keywords drugs ; agonists ; anxiety ; recruitment ; signal transduction ; proteins ; stress response
    Language English
    Document type Article
    ISSN 0960-894X
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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