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Article ; Online: Attenuated dopamine receptor signaling in nucleus accumbens core in a rat model of chemically-induced neuropathy.

Selley, Dana E / Lazenka, Matthew F / Sim-Selley, Laura J / Secor McVoy, Julie R / Potter, David N / Chartoff, Elena H / Carlezon, William A / Negus, S Stevens

Neuropharmacology

2020 Volume 166, Page(s) 107935

Abstract: Neuropathy is major source of chronic pain that can be caused by mechanically or chemically induced nerve injury. Intraplantar formalin injection produces local necrosis over a two-week period and has been used to model neuropathy in rats. To determine ... ...

Abstract	Neuropathy is major source of chronic pain that can be caused by mechanically or chemically induced nerve injury. Intraplantar formalin injection produces local necrosis over a two-week period and has been used to model neuropathy in rats. To determine whether neuropathy alters dopamine (DA) receptor responsiveness in mesolimbic brain regions, we examined dopamine D
MeSH term(s)	Animals ; Conditioning, Operant/drug effects ; Conditioning, Operant/physiology ; Disease Models, Animal ; Dopamine Agonists/pharmacology ; Dopamine Antagonists/pharmacology ; Dose-Response Relationship, Drug ; Formaldehyde/toxicity ; Male ; Neuralgia/chemically induced ; Neuralgia/metabolism ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D1/agonists ; Receptors, Dopamine D1/antagonists & inhibitors ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D2/agonists ; Receptors, Dopamine D2/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology
Chemical Substances	DRD2 protein, rat ; Dopamine Agonists ; Dopamine Antagonists ; Drd1 protein, rat ; Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Formaldehyde (1HG84L3525)
Language	English
Publishing date	2020-01-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2020.107935
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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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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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Article ; Online: 8-epi-Salvinorin B

Thomas A. Munro / Katharine K. Duncan / Richard J. Staples / Wei Xu / Lee-Yuan Liu-Chen / Cécile Béguin / William A. Carlezon Jr. / Bruce M. Cohen

Beilstein Journal of Organic Chemistry, Vol 3, Iss 1, p

crystal structure and affinity at the κ opioid receptor

2007 Volume 1

Abstract: There have been many reports of epimerization of salvinorins at C-8 under basic conditions, but little evidence has been presented to establish the structure of these compounds. We report here the first crystal structure of an 8-epi-salvinorin or ... ...

Abstract	There have been many reports of epimerization of salvinorins at C-8 under basic conditions, but little evidence has been presented to establish the structure of these compounds. We report here the first crystal structure of an 8-epi-salvinorin or derivative: the title compound, 2b. The lactone adopts a boat conformation with the furan equatorial. Several lines of evidence suggest that epimerization proceeds via enolization of the lactone rather than a previously proposed indirect mechanism. Consistent with the general trend in related compounds, the title compound showed lower affinity at the kappa opioid receptor than the natural epimer salvinorin B (2a). The related 8-epi-acid 4b showed no affinity.
Keywords	Science ; Q ; Organic chemistry ; QD241-441
Language	English
Publishing date	2007-01-01T00:00:00Z
Publisher	Beilstein-Institut
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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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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Article ; Online: It is time to take a stand for medical research and against terrorism targeting medical scientists.

Krystal, John H / Carter, Cameron S / Geschwind, Daniel / Manji, Husseini K / March, John S / Nestler, Eric J / Zubieta, Jon-Kar / Charney, Dennis S / Goldman, David / Gur, Raquel E / Lieberman, Jeffrey A / Roy-Byrne, Peter / Rubinow, David R / Anderson, Stewart A / Barondes, Samuel / Berman, Karen F / Blair, James / Braff, David L / Brown, E Sherwood /

Calabrese, Joseph R / Carlezon, William A / Cook, Edwin H / Davidson, Richard J / Davis, Michael / Desimone, Robert / Drevets, Wayne C / Duman, Ronald S / Essock, Susan M / Faraone, Stephen V / Freedman, Robert / Friston, Karl J / Gelernter, Joel / Geller, Barbara / Gill, Michael / Gould, Elizabeth / Grace, Anthony A / Grillon, Christian / Gueorguieva, Ralitza / Hariri, Ahmad R / Innis, Robert B / Jones, Edward G / Kleinman, Joel E / Koob, George F / Krystal, Andrew D / Leibenluft, Ellen / Levinson, Douglas F / Levitt, Pat R / Lewis, David A / Liberzon, Israel / Lipska, Barbara K / Marder, Stephen R / Markou, Athina / Mason, Graeme F / McDougle, Christopher J / McEwen, Bruce S / McMahon, Francis J / Meaney, Michael J / Meltzer, Herbert Y / Merikangas, Kathleen R / Meyer-Lindenberg, Andreas / Mirnics, Károly / Monteggia, Lisa M / Neumeister, Alexander / O'Brien, Charles P / Owen, Michael J / Pine, Daniel S / Rapoport, Judith L / Rauch, Scott L / Robbins, Trevor W / Rosenbaum, Jerrold F / Rosenberg, David R / Ross, Christopher A / Rush, A John / Sackeim, Harold A / Sanacora, Gerard / Schatzberg, Alan F / Shaham, Yavin / Siever, Larry J / Sunderland, Trey / Tecott, Laurence H / Thase, Michael E / Todd, Richard D / Weissman, Myrna M / Yehuda, Rachel / Yoshikawa, Takeo / Young, Elizabeth A / McCandless, R

Biological psychiatry

2007 Volume 63, Issue 8, Page(s) 725–727

MeSH term(s)	Animal Experimentation ; Animal Rights ; Animals ; Attitude of Health Personnel ; Biomedical Research ; Crime/prevention & control ; Ethics, Research ; Humans ; Primates ; Research Personnel ; Terrorism/prevention & control ; United States
Language	English
Publishing date	2007-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2008.03.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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 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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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 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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