Cocaine acute "binge" administration results in altered thalamocortical interactions in mice.
BACKGROUND
Abnormalities 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.


METHODS
Thalamocortical 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.


RESULTS
In vivo EEG recordings after cocaine "binge" administration showed a significant increment, compared with saline, 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 activation at more negative membrane potentials and increments in both I(h) 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 gamma-aminobutyric acid-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) overinhibition of VB neurons that can abnormally "lock" the whole thalamocortical system at low frequencies.
Urbano
Francisco J
FJ
Department of Physiology & Neuroscience, New York University School of Medicine, New York, New York, USA. fjurbano@fbmc.fcen.uba.ar
Bisagno
Verónica
V
Wikinski
Silvia I
SI
Uchitel
Osvaldo D
OD
Llinás
Rodolfo R
RR
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D013788:Thalamus / Q000187:drug effects* / Q000502:physiology
D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D003042:Cocaine