IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Cocaine acute “binge” administration increases thalamic GABAergic synaptic transmission in mice
Autor/es:
V. BISAGNO, M. RAINERI, S. I. WIKINSKI, O. D. UCHITEL, R. R. LLINAS, F. J. URBANO
Lugar:
McCormick Place, Chicago, U.S.A.
Reunión:
Congreso; 2009 Society for Neuroscience (SfN) Annual Meeting; 2009
Institución organizadora:
Society for Neuroscience
Resumen:
Characterization of the neurobiological substrates involved in attention, perception and sensory processing deficits in cocaine addicts is relevant to cocaine abuse treatment. Thalamocortical system is involved in sensory processing, however, little is known about possible mechanisms mediating cocaine effects on the thalamocortical circuitry. Thalamic ventrobasal nucleus (VB) is known to be densely innervated by GABAergic terminals from reticular neurons. Both reticular and VB neurons have LTS mediated by T-type calcium currents. Recent work (see Urbano et al., this meeting) indicates that cocaine “binge” administration increased activation of T-type channels on VB neurons at resting membrane potentials. Here we studied whether cocaine acute “binge” (3x15mg injections 1 h apart) would enhance GABAergic feed-back transmission from reticular to VB neurons.In vitro, voltage clamp recordings of VB thalamic neurons in the presence of TTX (3 μM), DL-AP5 (50 μM), CNQX (20 μM) showed higher levels of GABA-A-mediated synaptic transmission (i.e., blocked by both picrotoxin and bicuculline, 50 μM) lasting over 24 hours after last injection of cocaine. Indeed, miniature inhibitory postsynaptic currents (mIPSCs) recorded from VB neurons presented an increment in amplitudes and shorter inter-event intervals compared to saline, partially reverted after 24 hr. Also immunohistochemical experiments were performed on brain slices containing primary somatosensory cortex (S1) and thalamic nuclei using antibodies for Glutamic Acid Decarboxylase (GAD 65/67) in saline and cocaine groups. No significant differences were found on immunostaining levels. Similar to cocaine mediated effect on GABAergic transmission, bath application of the D2/D3-agonist Ropinirole (50 μM) enhanced GABA-A minis amplitudes while reducing their inter-event intervals. Also, bath application of T-type calcium channels blolckers NiCl2 (200 μM) or 2-Octanol (50 μM) blocked the enhancement of GABAergic minis frequency mediated by cocaine. Thus, these results suggest a possible role of D2/D3 receptors in VB’s GABA-A minis enhancement induced by cocaine. Also, higher number of T-currents-mediated LTS bursts at reticular neuron’s terminals might be responsible for the enhancement in GABAergic transmission onto the VB nucleus. Absence of changes on GAD immunostaining seems to indicate that GABAergic enhancement is not primarily due to changes in GABAergic terminals.