Effects of repeated cocaine (COC) administration on potassium channels in the core and shell of rat medium spiny nucleus accumbens (NAC) neurons

Orlando

Congreso; 2002 Society for Neuroscience Meeting; 2002

The NAC has long been recognized to be involved in motivational behaviors such as drug seeking and withdrawal. Our previous studies have indicated significant decreases in NAC neuronal excitability due to reduced voltage-sensitive Na+ and Ca2+ currents following repeated COC administration. Our present study seeks to determine the effects of repeated COC administration on K+ channel function in the NAC core and shell. Current clamp recordings were performed in visualized NAC neurons with in vitro slice preparation following repeated administration of COC (15 mg/kg, i.p.) for 5 days with a 3-day withdrawal. Pulse injections of hyperpolarizing currents (-0.05 to -0.8 nA) induced a significant depolarizing (upward) shift in the I-V curve in the NAC core of COC-pretreated rats as compared to saline controls. COC also significantly decreased the input resistance (Rin) of NAC neurons in the core. Such changes in the I-V curve and Rin were not observed in the NAC shell. Other studies have shown that blockade of inward rectifying K+ (IRK) currents by barium (Ba2+) causes increased hyperpolarization during negative current pulse injections. At -0.5 nA current, Ba2+ (100 μM) application significantly increased the percentage change from basal membrane potential in NAC core of COC-pretreated rats as compared to saline controls, suggesting an increase in Ba2+ sensitive IRK currents in COC pretreated rats. The depolarizing shift in NAC core neurons was eliminated after 2 to 3 weeks of withdrawal from COC administration. The effects of COC on outward rectifying K+ channels are currently under investigation