COCAINE ACUTE “BINGE” ADMINISTRATION RESULTS IN ALTERED INTRINSIC PROPERTIES OF THALAMOCORTICAL NEURONS IN MICE.

URBANO FJ; BISAGNO V; WIKINSKI S; UCHITEL O; LLINAS R

Chicago, EEUU

Congreso; Neurosciences 2009; 2009

Society for Neurosciences

Cocaine acute “binge” administration results in altered intrinsic properties of thalamocortical neurons in mice. Francisco J. Urbano1, Verónica Bisagno2, Silvia I. Wikinski2, Osvaldo D. Uchitel1 and Rodolfo R. Llinás3 1 Laboratorio de Fisiología y Biología Molecular, Instituto de Fisiología, Biología Molecular y Neurociencias (LFBM-IFIBYNE), CONICET-UBA, Intendente Guiraldes 2670, pabellón 2, piso 2, Ciudad Universitaria, C1428BGA-Buenos Aires, Argentina. fjurbano@fbmc.fcen.uba.ar. Phone: (+54-11) 4576 3368; fax: (+54-11) 4576 3321. 2 Instituto de Investigaciones Farmacológicas (ININFA- CONICET-UBA), Junín 956, piso 5, C1113-Buenos Aires, Argentina. Phone: (+54-11) 4961 6784. vbisagno@ffyb.uba.ar. 3 Department of Physiology & Neuroscience, New York University School of Medicine, 550 First Avenue, NY10016, New York, USA. Phone: (+1-212) 263 5415. Rodolfo.Llinas@nyumc.org. Abnormalities in both thalamic and cortical areas have been reported in human cocaine addicts using non-invasive functional MRI. Abnormal thalamocortical rhythms play an important role in the pathophysiology of different neurological and neuropsychiatric diseases, including Parkinson’s disease, schizophrenia, etc., named thalamocortical dysrhythmia syndrome. Since thalamocortical activity is the product of the intrinsic properties of thalamic neurons, their recurrent connectivity with the cortex and the synaptic input from sensory and mesencephalic neurons, we studied thalamocortical function both in vivo and in vitro in mice one hour following i.p. saline or cocaine “binge” administration (3x15mg/Kg, one hour apart), as well as 24 hours after last cocaine injection. Compared to saline, in vivo EEG recordings following cocaine “binge” administration showed a significant increment in low frequencies (reversible after 24 hours), while observing no changes in high frequency gamma activity. In vitro voltage- and current-clamp patch recordings from VB neurons after cocaine “binge” administration showed low threshold spikes (LTS) activation at more negative membrane potentials; and increments in both Ih and low voltage activated T-type calcium currents (CaV3 mediated). Also, a 10 mV negative shift on threshold activation level of T-type current was observed. In conclusion, our results showed an atypically higher activation of T-type calcium currents present on VB relay neurons from cocaine “binge” treated mice, that would increase low frequency oscillatory thalamocortical activity. Thus, suggesting that cocaine acute “binge” induced a transitory thalamocortical dysrhythmia-like state. This work was supported by Grants from: FONCYT (ANPCyT) PICT 2007-01009 (to Dr. Urbano), Wellcome Trust, 068941/Z/02/Z; ANCyT; grant#6220; UBACYT; grant# X171 & X223; FONCYT (ANPCyT) PICT2005-32113 & 13367, & PICT2006-199 (to Dr. Uchitel), National Institutes of Health NS13742 (to Dr. Llinás) and PICT 31953 (ANPCyT), PIP 5870 (CONICET) and UBACYT M073 (to Dr. Wikinski).