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

Psychopharmacology
Verónica BisagnoFrancisco J Urbano

Abstract

Repetitive cocaine exposure has been shown to induce GABAergic thalamic alterations. Given the key role of T-type (Ca(V)3) calcium channels in thalamocortical physiology, the direct involvement of these calcium channels in cocaine-mediated effects needs to be further explored. 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. 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 x 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. 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 ...Continue Reading

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Citations

Feb 10, 2016·Neurotoxicity Research·Javier A MuñizVeronica Bisagno
Nov 15, 2011·Journal of Physiology, Paris·Osvaldo D UchitelMariano N Di Guilmi
Jan 19, 2016·Sleep Science·Francisco J UrbanoEdgar Garcia-Rill
Dec 5, 2012·Journal of Neurochemistry·Belén GoitiaFrancisco J Urbano
Mar 29, 2014·Frontiers in Behavioral Neuroscience·Giuseppe GangarossaEmmanuel Valjent
Mar 1, 2014·Biophysics Reviews·Osvaldo D UchitelMariano N Di Guilmi
Nov 27, 2020·Psychopharmacology·María Celeste Rivero-EchetoFrancisco J Urbano

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