CONICET | Buscador de Institutos y Recursos Humanos

Our group previously described that a cocaine binge(3x15 mg/kg, 1h apart; slices were obtained 1 hour after last injection) induces an enhancement in both GABAergic transmission and T-type calcium currents on Ventrobasal (VB) thalamic neurons. Such effects were prevented by the systemic administration of T-type calcium channel antagonists mibefradil and 2-octanol. However, it is unknown if protein levels of the enzyme that synthesizes GABA (glutamic acid decarboxylase isoforms GAD65/67) or T-type calcium channel subunits (Cav3.1 and 3.3) are affected by a cocaine binge. The objective of this study was to assess the effects of acute and chronic cocaine binge administration on protein levels relative to actin levels and compared to saline administration, of GAD65/67, Cav3.1 and Cav3.3 T-type calcium channel subunits using Western Blotting. No changes in the levels of these proteins were observed in either VB or Reticular (Ret) nuclei 1 hour after a cocaine binge administration (MANOVA for VB and Ret, p>0.05). Similarly, no changes were observed 24 hours after the last binge injection (MANOVA for VB and Ret, p>0.05). However, one day after a chronic binge protocol (one binge a day, for 3 days) an increase in protein levels of Cav3.1 was observed in the VB nucleus (Mean±S.E.M., cocaine=318%±69, n=4; saline=100%±34, n=6; ANOVA p=0.0131). No changes in GAD65/67 levels were found. After a fourth binge administration, no changes were observed in VB Cav 3.1 protein levels. Instead, GAD67 levels were increased in Ret nucleus (1 hour after the fourth binge, cocaine=156%±29, n=4 mice; saline= 100±18, n=3 mice; ANOVA p=0.024). No differences were found in GAD65/67 protein levels in the VB nucleus. In conclusion, T- type and GAD65/67 protein levels were increased by chronic cocaine administration. Changes in the expression levels of these two key proteins may help explain the alterations observed in thalamocortical networks of long-term cocaine abusers.