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Abstract:

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.

Registro:

Documento: Artículo
Título:Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice
Autor:Bisagno, V.; Raineri, M.; Peskin, V.; Wikinski, S.I.; Uchitel, O.D.; Llinás, R.R.; Urbano, F.J.
Filiación:Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Junín 956, piso 5, C1113 Buenos Aires, Argentina
Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Ciudad Universitaria, Intendente Guiraldes 2670, pabellón 2, piso 2, C1428BGA Buenos Aires, Argentina
Palabras clave:2-octanol; Cocaine; GABA; Locomotor activity; Mibefradil; Nickel; T-type calcium channels; Thalamocortical; Ventrobasal nucleus; 2 octanol; calcium channel T type; cocaine; mibefradil; nickel; animal behavior; animal experiment; animal tissue; article; brain nerve cell; controlled study; dose response; drug mechanism; drug megadose; GABAergic transmission; in vitro study; in vivo study; locomotion; low drug dose; male; mouse; nonhuman; priority journal; thalamocortical tract; thalamus ventral nucleus; Animals; Calcium Channel Blockers; Calcium Channels, T-Type; Cocaine; Dose-Response Relationship, Drug; Drug Administration Schedule; gamma-Aminobutyric Acid; Locomotion; Male; Mibefradil; Mice; Mice, Inbred C57BL; Nickel; Octanols; Patch-Clamp Techniques; Thalamus
Año:2010
Volumen:212
Número:2
Página de inicio:205
Página de fin:214
DOI: http://dx.doi.org/10.1007/s00213-010-1947-z
Título revista:Psychopharmacology
Título revista abreviado:Psychopharmacology
ISSN:00333158
CODEN:PSCHD
CAS: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
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00333158_v212_n2_p205_Bisagno

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Citas:

---------- APA ----------
Bisagno, V., Raineri, M., Peskin, V., Wikinski, S.I., Uchitel, O.D., Llinás, R.R. & Urbano, F.J. (2010) . Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice. Psychopharmacology, 212(2), 205-214.
http://dx.doi.org/10.1007/s00213-010-1947-z
---------- CHICAGO ----------
Bisagno, V., Raineri, M., Peskin, V., Wikinski, S.I., Uchitel, O.D., Llinás, R.R., et al. "Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice" . Psychopharmacology 212, no. 2 (2010) : 205-214.
http://dx.doi.org/10.1007/s00213-010-1947-z
---------- MLA ----------
Bisagno, V., Raineri, M., Peskin, V., Wikinski, S.I., Uchitel, O.D., Llinás, R.R., et al. "Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice" . Psychopharmacology, vol. 212, no. 2, 2010, pp. 205-214.
http://dx.doi.org/10.1007/s00213-010-1947-z
---------- VANCOUVER ----------
Bisagno, V., Raineri, M., Peskin, V., Wikinski, S.I., Uchitel, O.D., Llinás, R.R., et al. Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice. Psychopharmacology. 2010;212(2):205-214.
http://dx.doi.org/10.1007/s00213-010-1947-z