Cocaine-induced plasticity of intrinsic membrane properties in prefrontal cortex pyramidal neurons: Adaptations in potassium currents

Drug- induced adaptations in the prefrontal cortex ( PFC) contribute to several core aspects of addictive behaviors, but the underlying neuronal processes remain essentially unknown. Here, we demonstrate that repeated in vivo exposure to cocaine persistently reduces the voltage- gated K (+) current ( VGKC) in PFC pyramidal neurons, resulting in enhanced membrane excitability. Analysis of dopamine D-1- class receptor ( D1R)- mediated modulation of VGKC indicates that, despite the absence of direct D1R stimulation, downstream D-1 signaling ( the cAMP/ protein kinase A pathway) is increased during withdrawal from chronic cocaine treatment and plays a central role in the drug- induced membrane plasticity in PFC. This long- lasting, cocaine- induced plasticity of membrane excitability in PFC pyramidal neurons may contribute to the impaired decision making and drug craving that characterize cocaine withdrawal.