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

Abstract

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.

The Novel Cognitive Enhancer ST101 Enhances Acetylcholine Release in Mouse Dorsal Hippocampus Through T-type Voltage-Gated Calcium Channel Stimulation

“…Since mibefradil (20 mg/kg, i.p.) inhibits cocaine-induced hyperlocomotion in vivo 90 min after intraperitoneal administration in mice (18) and induces antinociception 60 -120 min after intraperitoneal administration (3 -9 mg/kg) in rats (19), mibefradil was injected intraperitoneally 90 min before ST101 treatment. We observed a significant group effect on alternation behavior in the Y-maze task [F(8,61) = 2.09, P < 0.01].…”

“…Mibefradil (5 -10 μM) treatment significantly inhibits T-type VGCC-regulated GABA-A-mediated synaptic transmission in vitro (18). Based on the previous studies, we investigated the effects of a T-type calcium channel inhibitor, mibefradil, on ST101-induced ACh release in dorsal hippocampus.…”

Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum

“…Total distance traveled (in cm) was quantified in 5-min bins for a total of 180 min after the first injection (i.e., 60 min were recorded after each of the three drug injections). Behavioral recordings were made simultaneously in four open-field arenas using the Ethovision XT multiple arena feature from 9 AM to 4 PM of the light period of the light/dark cycle, similar to a previously published study (Bisagno et al 2010). Injection time and arenas (right and left) were counterbalanced across experimental groups.…”

Methamphetamine blunts Ca2+currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex

“…At 4 day of METH withdrawal, control or METH/SCH23390 treated mice were deeply anesthetized with tribromoethanol (250 mg/Kg; i.p. ) followed by transcardial perfusion with ice-cold low sodium/antioxidants solution (composition in mM: 200 sucrose, 2.5 KCl, 3 MgSO 4 , 26 NaHCO 3 , 1.25 NaH 2 PO 4 , 20 d-glucose, 0.4 ascorbic acid, 2 pyruvic acid, 1 kynurenic acid, 1 CaCl 2 , and aerated with 95% O 2 /5% CO 2 , pH 7.4), and then decapitated as previously described (Urbano et al, 2009; Bisagno et al, 2010). Coronal brain slices, including mPFC (300 μm) were obtained gluing both hemispheres with the caudal part onto a vibrotome aluminum stage (Integraslicer 7550 PSDS, Campden Instruments, UK), submerged in a chamber containing chilled low-sodium/high-sucrose solution (composition in mM: 250 sucrose, 2.5 KCl, 3 MgSO 4 , 0.1 CaCl 2 , 1.25 NaH 2 PO 4 , 0.4 ascorbic acid, 3 myo-inositol, 2 pyruvic acid, 25 d-glucose, and 25 NaHCO 3 ).…”

“…Coronal brain slices, including mPFC (300 μm) were obtained gluing both hemispheres with the caudal part onto a vibrotome aluminum stage (Integraslicer 7550 PSDS, Campden Instruments, UK), submerged in a chamber containing chilled low-sodium/high-sucrose solution (composition in mM: 250 sucrose, 2.5 KCl, 3 MgSO 4 , 0.1 CaCl 2 , 1.25 NaH 2 PO 4 , 0.4 ascorbic acid, 3 myo-inositol, 2 pyruvic acid, 25 d-glucose, and 25 NaHCO 3 ). Slices were cut sequentially and transferred to an incubation chamber at 37°C for 30 min containing a low Ca 2+ /high Mg 2+ normal ACSF (composition in mM: 125 NaCl, 2.5 KCl, 3 MgSO 4 , 0.1 CaCl 2 , 1.25 NaH 2 PO 4 , 0.4 ascorbic acid, 3 myo-inositol, 2 pyruvic acid, 25 d-glucose, and 25 NaHCO 3 and aerated with 95% O 2 /5% CO 2 , pH 7.4; Urbano et al, 2009, Bisagno et al, 2010). After incubation, slices were allowed to return to room temperature.…”