Effects of repeated cocaine (COC) administration on high voltage activated (HVA)-Ca2+ potentials in medial prefrontal cortex pyramidal (mPFC) neurons

Orlando

Congreso; 2002 Society for Neuroscience Meeting; 2002

Our previous findings indicate that repeated administration of COC increases excitability of mPFC neurons. This change is caused, at least partially, by a decrease in voltage-gated outward K+ currents. However, the function of other membrane ion channels, such as HVA-Ca2+ channels, may also be altered by repeated administration of COC. This study was conducted to determine if changes in HVA-Ca2+ potentials in mPFC neurons are present following 5 days of COC pretreatment and 3 days of withdrawal. Current-clamp recordings were used in vitro with rat brain slices. Ca2+ plateau potentials typically have a length of duration more than 2 s and stepwise repolarization (usually 2 steps). The repolarization in steps has been related to a nonhomogeneous distribution of HVA-Ca2+ channels. Previous studies suggests that, the first (larger) step is associated with proximally located HVA-Ca2+ channels while the lower step is generated by Ca2+ channels located distally in the dendrites. The duration of HVA-Ca2+ potentials were significantly increased (29%) in mPFC neurons following repeated COC pretreatment as compared to saline-pretreated cells. This change was mainly due to an increased duration in the first, but not the second, step. These results suggest that repeated COC administration might increase the function of HVA-Ca2+ channels located in, or proximal to, the soma of mPFC neurons that could contribute to the increase of neuronal excitability. The types of HVA-Ca2+ channels involved in COC-induced changes in the duration of Ca2+ potentials are currently under investigation.