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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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00333158_v212_n2_p205_Bisagno http://hdl.handle.net/20.500.12110/paper_00333158_v212_n2_p205_Bisagno |
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paper:paper_00333158_v212_n2_p205_Bisagno2023-06-08T15:00:27Z Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice 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 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. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00333158_v212_n2_p205_Bisagno http://hdl.handle.net/20.500.12110/paper_00333158_v212_n2_p205_Bisagno |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice |
| topic_facet |
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 |
| description |
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. |
| title |
Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice |
| title_short |
Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice |
| title_full |
Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice |
| title_fullStr |
Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice |
| title_full_unstemmed |
Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice |
| title_sort |
effects of t-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical gabaergic abnormalities in mice |
| publishDate |
2010 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00333158_v212_n2_p205_Bisagno http://hdl.handle.net/20.500.12110/paper_00333158_v212_n2_p205_Bisagno |
| _version_ |
1768544900915134464 |