Archival ReportCocaine Acute “Binge” Administration Results in Altered Thalamocortical Interactions in Mice

BackgroundAbnormalities in both thalamic and cortical areas have been reported in human cocaine addicts with noninvasive functional magnetic resonance imaging. 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.MethodsThalamocortical function was studied in vivo and in vitro in mice after cocaine “binge” administration. In vivo awake electroencephalography (EEG) was implemented in mice injected with saline, 1 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.ResultsIn vivo EEG recordings after cocaine “binge” administration showed a significant increment, compared with saline, in low frequencies while observing no changes in high-frequency γ activity. In vitro patch recordings from VB neurons after cocaine “binge” administration showed low threshold spikes 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 γ-aminobutyric acid-A-mediated minis were observed.ConclusionsOur 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) overinhibition of VB neurons that can abnormally “lock” the whole thalamocortical system at low frequencies.