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 D1-class receptor (D1R)-mediated modulation of VGKC indicates that, despite the absence of direct D1R stimulation, downstream D1 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.
Dong
Yan
Y
Department of Neuroscience, The Chicago Medical School, North Chicago, Illinois 60064, USA. yan_dong@merck.com
Nasif
Fernando J
FJ
Tsui
Jennifer J
JJ
Ju
William Y
WY
Cooper
Donald C
DC
Hu
Xiu-Ti
XT
Malenka
Robert C
RC
White
Francis J
FJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D009044:Motor Cortex / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D024642:Potassium Channels, Voltage-Gated; D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D003042:Cocaine