Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice
Rationale: Repetitive cocaine exposure has been shown to induce GABAergic thalamic alterations. Given the key role of T-type (CaV3) calcium channels in thalamocortical physiology, the direct involvement of these calcium channels in cocaine-mediated effects needs to be further explored. Objective: Th...
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2010
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| LEADER | 25585caa a22018737a 4500 | ||
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| 001 | PAPER-22822 | ||
| 003 | AR-BaUEN | ||
| 005 | 20230518205425.0 | ||
| 008 | 190411s2010 xx ||||fo|||| 00| 0 eng|d | ||
| 024 | 7 | |2 scopus |a 2-s2.0-77957341755 | |
| 024 | 7 | |2 cas |a 2 octanol, 123-96-6; cocaine, 50-36-2, 53-21-4, 5937-29-1; mibefradil, 116666-63-8; nickel, 7440-02-0; 2-octanol, 123-96-6; Calcium Channel Blockers; Calcium Channels, T-Type; Cocaine, 50-36-2; Mibefradil, 116644-53-2; Nickel, 7440-02-0; Octanols; gamma-Aminobutyric Acid, 56-12-2 | |
| 040 | |a Scopus |b spa |c AR-BaUEN |d AR-BaUEN | ||
| 030 | |a PSCHD | ||
| 100 | 1 | |a Bisagno, V. | |
| 245 | 1 | 0 | |a Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice |
| 260 | |c 2010 | ||
| 270 | 1 | 0 | |m Llinás, R. R.; Department of Physiology and Neuroscience, New York University, School of Medicine, 550 First Avenue, New York, NY 10016, United States; email: Rodolfo.Llinas@nyumc.org |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a Rationale: Repetitive cocaine exposure has been shown to induce GABAergic thalamic alterations. Given the key role of T-type (CaV3) calcium channels in thalamocortical physiology, the direct involvement of these calcium channels in cocaine-mediated effects needs to be further explored. Objective: The objective of this study was to investigate the effect of T-type calcium channel blockers on acute and repetitive cocaine administration that mediates thalamocortical alterations in mice using three different T-type blockers: 2-octanol, nickel, and mibefradil. Methods: During in vitro experiments, whole-cell patch-clamp recordings were conducted in ventrobasal (VB) thalamic neurons from mice treated with acute repetitive cocaine administration (3∈×∈15 mg/kg, i.p., 1 h apart), under bath application of mibefradil (10 μM), 2-octanol (50 μM), or nickel (200 μM). After systemic administration of T-type calcium channel blockers, we evaluated locomotor activity and also recorded GABAergic neurotransmission onto VB neurons in vitro. Results: Bath-applied mibefradil, 2-octanol, or nickel significantly reduced both GABAergic neurotransmission and T-type currents of VB neurons in cocaine-treated mice. In vivo i.p. pre-administration of either mibefradil (20 mg/kg and 5 mg/kg) or 2-octanol (0.5 mg/kg and 0.07 mg/kg) significantly reduced GABAergic mini frequencies onto VB neurons. Moreover, both mibefradil and 2-octanol were able to decrease cocaine-induced hyperlocomotion. Conclusion: The results shown in this study strongly suggest that T-type calcium channels play a key role in cocaine-mediated GABAergic thalamocortical alterations, and further propose T-type channel blockers as potential targets for future pharmacological strategies aimed at treating cocaine's deleterious effects on physiology and behavior. © 2010 Springer-Verlag. |l eng | |
| 536 | |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica | ||
| 536 | |a Detalles de la financiación: Inter-American Development Bank, PICT 2007-1009, PICT 2008-2019 | ||
| 536 | |a Detalles de la financiación: Secretaría de Ciencia y Técnica, Universidad de Buenos Aires, X171 | ||
| 536 | |a Detalles de la financiación: Wellcome Trust, 068941/Z/02/Z | ||
| 536 | |a Detalles de la financiación: 6220 | ||
| 536 | |a Detalles de la financiación: Fondo para la Investigación Científica y Tecnológica | ||
| 536 | |a Detalles de la financiación: Acknowledgments The authors would like to thank Maria Eugenia Martin and Paula Felman for their excellent technical and administrative assistance, Dr. Carina Weissmann for proofreading our manuscripts, and Dr. Joaquin Piriz for his critical reading of our work. Dr. Bisagno has been authorized to study drug-abuse substances in animal models by the National Board of Medicine Food and Medical Technology, Ministerio de Salud, Argentina (A.N.M.A.T). This work was supported by grants from: FONCyT, Agencia Nacional de Promoción Científica y Tecnológica; BID 1728 OC.AR. PICT 2007-1009, PICT 2008-2019 and PIDRI-PRH 2007 (to Dr. Urbano), Wellcome Trust, grant # 068941/Z/02/Z; ANCyT; grant # 6220; UBACYT; grant # X171, and X223; FONCyT, Agencia Nacional de Promoción Científica y Tecnológica; BID 1728 OC.AR. PICT2005 #32,113 and #13,367; and BID 1728 OC.AR. PICT 2006 # 199 (to Dr. Uchitel), National Institutes of Health NS13742 (to Dr. Llinás) and PICT 31953 (ANPCyT) and UBACYT M073 (to Dr. Wikinski). | ||
| 593 | |a Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Junín 956, piso 5, C1113 Buenos Aires, Argentina | ||
| 593 | |a Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Ciudad Universitaria, Intendente Guiraldes 2670, pabellón 2, piso 2, C1428BGA Buenos Aires, Argentina | ||
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| 700 | 1 | |a Raineri, M. | |
| 700 | 1 | |a Peskin, V. | |
| 700 | 1 | |a Wikinski, S.I. | |
| 700 | 1 | |a Uchitel, O.D. | |
| 700 | 1 | |a Llinás, R.R. | |
| 700 | 1 | |a Urbano, F.J. | |
| 773 | 0 | |d 2010 |g v. 212 |h pp. 205-214 |k n. 2 |p Psychopharmacology |x 00333158 |t Psychopharmacology | |
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