COCAINE ACUTE “BINGE” ADMINISTRATION RESULTS IN ALTERED THALAMOCORTICAL INTERACTIONS IN MICE

URBANO FJ, BISAGNO V, WIKINSKI SI, UCHITEL OD & LLINAS RR

BIOLOGICAL PSYCHIATRY

Elsevier B.V.

Lugar: Amsterdam, New York; Año: 2009 p. 769 - 776

0006-3223

Background: Abnormalities in both thalamic and cortical areas have been reported in human cocaine addicts using non-invasive functional MRI. Given the substantial involvement of the thalamocortical system in sensory processing and perception we defined electrophysiology-based protocols to attempt a characterization of cocaine effects on thalamocortical circuits. Methods: Thalamocortical function was studied in vivo and in vitro in mice following i.p. cocaine “binge” administration. In vivo awake EEG was implemented in mice injected with saline, one hour or 24 hours after the last cocaine “binge” injection. In vitro current- and voltage-clamp whole-cell patch-clamp recordings were performed from slices including thalamic relay ventrobasal (VB) neurons. Results: Compared to saline, in vivo EEG recordings following cocaine “binge” administration showed a significant increment in low frequencies while observing no changes in high frequency gamma activity. In vitro 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. Also, a 10 mV negative shift on threshold activation level of T-type current and a remarkable increment in both frequency and amplitudes of GABA-A-mediated minis were observed. Conclusions: Our data indicate that thalamocortical dysfunctions observed in cocaine abusers might be due to two distinct but additive events: 1) increased low frequency oscillatory thalamocortical activity and 2) over-inhibition of VB neurons that can abnormally “lock” the whole thalamocortical system at low frequencies.