Cocaine “binge” administration alters inhibitory networks in somatosensory cortical slices from mice.

URBANO FJ; HYDE JR; FANTEGROSSI WE; BISAGNO V; GARCIA-RILL E

Washington DC, USA, Nov 12-16, 2011

Congreso; 41th Society for Neuroscience Annual Meeting; 2011

Society for Neuroscience

We previously described abnormal thalamic GABAergic transmission in mice administered repetitively with cocaine. Here we used voltage-sensitive dye imaging (VSDI) to test how cortical networks are affected by cocaine “binge-like” (i.p.; 3x15mg/kg, 1 hour apart) treatment in coronal slices (400 microm) obtained from juvenile mice (30-50 days old). Slices were stained over 20 minutes with 400 microM di-4ANEPPS (Molecular Probes, Eugene, OR) and placed in an interface chamber (BSC-1, Scientific Systems Design, Canada). Emitted fluorescent light was quantified with a 512x512 pixel back illuminated EMCCD Evolve 512 (Photometrics, AZ) camera. Optical recordings were acquired and analyzed with MetaMorph software (Molecular Devices, CA). A field potential electrode located in cortical layer IV was used. Two concentric bipolar electrodes separated 1-1.5 mm were used to deliver 10 Hz (4 shocks) and 40 Hz (15 shocks) train stimulation at the edge of the white matter. Slices from control, saline injected mice displayed fluorescence changes that spread from the white matter to the upper layers. The GABA-A receptor antagonist gabazine (50 microM) increased both area and amplitude for VSDI and field potential signals (n=4 slices). However, However, gabazine effects on cortical slices were blunted in slices obtained from mice administered a cocaine “binge” (n=3 slices).. Also, abnormal cortical activation during joint stimulation at 10Hz and 40Hz (“edge-effect”) was observed in slices from cocaine treated mice. Our results suggest that repetitive cocaine administration might alter somatosensory inhibitory cortical networks. Thus, suggesting a possible mechanism for the alterations in cortical activation observed in cocaine addicts.