Repeated cocaine administration alters the membrane responses of mPFC pyramidal neurons to hyperpolarizing current pulses

San Diego

Congreso; 2001 Society for Neuroscience Meetin; 2001

The medial prefrontal cortex (mPFC) is involved in acquisition of cocaine self-administration and in several aspects of the addictive processes. However, little is known about how cocaine affects activity of these neurons. We have previously reported that repeated administration of cocaine significantly decreases whole-cell Na+ (INa)and Ca2+ conductance in medium spiny neurons of the rat nucleus accumbens. Our preliminary study also determined a reduction in INa in acutely dissociated mPFC pyramidal neurons from layers V-VI in cocaine-pretreated rats. This change is associated with a depolarizing shift in the voltage-dependence of INa activation, indicating a decrease in membrane excitability of mPFC neurons. We are currently performing current clamp recordings from rat brain slices in vitro to characterize further alterations in the membrane properties of mPFC pyramidal neurons, particularly at hyperpolarized membrane potentials, following repeated cocaine treatment. Following five daily injections of cocaine (15 mg/kg i.p.) and 3 days of withdrawal, we observed marked alterations in the voltage responses of mPFC neurons to pulse injection of hyperpolarizing currents (-0.05 to -0.3 nA). Current-voltage (I-V) curves were significantly shifted in a hyperpolarized direction. The input resistance was also increased in cocaine-pretreated mPFC neurons. These findings suggest that the inward rectifying currents, such as Ih and K+, may be functionally altered following repeated cocaine administration. The inward rectifying currents that contribute to these alterations are now under investigation.