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Effects of T-type calcium channel blockers on cocaine-induced hyperlocomotion and thalamocortical GABAergic abnormalities in mice.

Authors :
Bisagno, Verónica
Raineri, Mariana
Peskin, Viviana
Wikinski, Silvia I.
Uchitel, Osvaldo D.
Llinás, Rodolfo R.
Urbano, Francisco J.
Source :
Psychopharmacology. Oct2010, Vol. 212 Issue 2, p205-214. 10p. 4 Graphs.
Publication Year :
2010

Abstract

Rationale: Repetitive cocaine exposure has been shown to induce GABAergic thalamic alterations. Given the key role of T-type (Ca3) 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00333158
Volume :
212
Issue :
2
Database :
Academic Search Index
Journal :
Psychopharmacology
Publication Type :
Academic Journal
Accession number :
53505410
Full Text :
https://doi.org/10.1007/s00213-010-1947-z