Repeated cocaine administration increases L-type calcium channel protein levels in rat medial prefrontal cortex (mPFC)

Washington DC

Congreso; 2005 Society for Neuroscience Meeting; 2005

Although the mPFC plays a critical role in cocaine addiction, little is known about how the activity of mPFC pyramidal neurons is affected by chronic exposure to this drug. Previous studies reveal that repeated cocaine administration decreases neuronal activity in the orbital frontal cortex (including the mPFC) of drug abusers during withdrawal. However, this suppressing effect of chronic cocaine on cortical activity is reversed and significantly enhanced when the withdrawn abusers are challenged with a cocaine-like drug or drug-related memory. Correspondingly, our recent findings also indicate that the excitability of mPFC pyramidal neurons in drug-withdrawn rats is increased in response to certain excitatory stimuli. This change in mPFC excitability has been attributed to an increase in influx of L-type Ca2+currents, along with a reduction in voltage-gated K+ currents. Based on these findings, this study was designed and performed to determine if the increased L-type Ca2+ currents in mPFC neurons can be attributed to an increased expression of the Ca2+ channel protein. Rats were injected with cocaine (15 mg/kg/day; i.p) or saline (0.1 ml/100g) for 5 consecutive days. Following 3 days of withdrawal, we used Western blots to analyze the protein levels of different types of voltage-gated Ca2+ channels in the mPFC. A significant increase in protein levels of the L-type Ca2+ channel was found in the cocaine-withdrawn mPFC as compared to that in saline-pretreated rats. This change was only seen in the particulate fraction, indicating that the increased expression of L channels occurred in the membrane. There was no significant change in the protein levels of other type Ca2+ channels in cocaine-withdrawn mPFC. These results indicate that the enhancement of L-type Ca2+ currents in response to membrane depolarization in cocaine-withdrawn mPFC neurons could be attributed to an increased expression of the L-type Ca2+ channel protein