IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
“Differential effects of acute cocaine and methylphenidate on thalamocortical gabaergic transmission. The role of thalamic T-type calcium channels ”
Autor/es:
BISAGNO V., RAINERI M., PESKIN V., GOITIA B., WIKINSKI S.I., UCHITEL O.D., URBANO F.J.
Lugar:
San Diego, Nov. 13-17.
Reunión:
Congreso; 40th Annual Meeting Society for Neuroscience; 2010
Institución organizadora:
Society for Neuroscience
Resumen:
A number of thalamocortical abnormalities have been found in cocaine addicts. We have recently reported that mice treated with an acute cocaine binge showed over activation of T-type calcium channels on thalamic Ventrobasal (VB) neurons at resting membrane potentials and also profound increments of GABAergic thalamic transmission. At least part of cocaine effects are due to its monoaminergic actions. Methylphenidate (MPH), a psychostimulant widely prescribed to treat ADHD, is a dopamine transporter and a norepinephrine transporter inhibitor but differs from cocaine in the fact that it does not bind to the serotonin transporter. In order to compare cocaine and MPH effects on the thalamocortical system, we aimed to study GABAergic minis and calcium currents of VB thalamic neurons from mice injected with MPH binge (MPH HCl; 3x15 and 30mg/kg, i.p., one hour apart) and cocaine binge (Cocaine HCl; 3x15 and 30 mg/kg, i.p., one hour apart) or saline. GABAergic minis cumulative intervals on VB neurons from MPH binge injected mice were smaller (i.e., indicating bigger GABAergic miniature frequencies) than saline, but smaller than cocaine binge injected animals (ANOVA, P<0.001). Also, low and high-voltage activated calcium currents ratios (LVA/HVA ratios) were not significantly affected by MPH binge (ANOVA, P>0.05). Bath applied T-type calcium blockers: mibefradil (10 μM), 2-octanol (50 μM) or nickel (200 μM) significantly reduced both GABAergic neurotransmission and T-type currents of VB neurons from cocaine binge treated mice, without affecting GABAergic transmission from saline mice (ANOVA, P<0.001). These results suggest that T-type calcium channel blockers might be beneficial on cocaine addiction treatment and further suggest a key role of serotonin on thalamocortical alterations induced by cocaine. Acknowledgments: Dr. Bisagno has been authorized by A.N.M.A.T. (Ministerio de Salud, Argentina) to study drug abuse substances in animal models. This work was supported by: ANPCyT BID 1728 OC.AR PICT 2007-1009, PICT 2008-2019 and PIDRI-PRH 2007 (to Dr. Urbano), Wellcome Trust, grant# 068941/Z/02/Z; ANCyT; grant#6220; UBACYT X171 and X223; ANPCyT BID 1728 OC.AR. PICT 2005-32113; and BID OC AR PICT 2006-199 (to Dr. Uchitel), and ANPCyT- BID OC.AR PICT 31953 and UBACYT M073 (to Dr. Wikinski).