title: Repeated cocaine administration increases voltage-sensitive calcium currents in response to membrane depolarization in medial prefrontal cortex pyramidal neurons.
abstract: The medial prefrontal cortex (mPFC) plays a critical role in cocaine addiction. However, evidence to elucidate how the mPFC is functionally involved in cocaine addiction remains incomplete. Recent studies have revealed that repeated cocaine administration induces various neuroadaptations in pyramidal mPFC neurons, including a reduction in voltage-gated K+ currents (VGKCs) and a possible increase in voltage-sensitive Ca2+ currents (I(Ca)). Here, we performed both current-clamp recordings in brain slices and voltage-clamp recordings in freshly dissociated cells to determine whether I(Ca) is altered in mPFC pyramidal neurons after chronic cocaine treatment with a short-term or long-term withdrawal. In addition, a critical role of VGKCs in regulating the generation of Ca2+ plateau potential was also studied in mPFC neurons. Repeated cocaine administration significantly prolonged the duration of evoked Ca2+ plateau potentials and increased the whole-cell I(Ca) in mPFC neurons after a 3 d withdrawal. Selective blockade of L-type Ca2+ channels by nifedipine not only significantly increased the threshold but also reduced the duration and amplitude of Ca2+ plateau potentials in both saline- and cocaine-withdrawn mPFC neurons. However, there was no significant difference in the increased threshold, reduced duration, and decreased amplitude of Ca2+ potentials between saline- and cocaine-withdrawn neurons after blockade of L-type Ca2+ channels. Moreover, an increase in amplitude was also observed, whereas the prolonged duration persisted, in Ca2+ potentials after 2-3 weeks of withdrawal. These findings indicate that chronic exposure to cocaine facilitates the responsiveness of I(Ca), particularly via the activated L-type Ca2+ channels, to excitatory stimuli in rat mPFC pyramidal neurons.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, North Chicago, Illinois 60064, USA.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Nasif
authors.forename: Xiu-Ti
authors.initials: XT
authors.lastname: Hu
authors.forename: Francis J
authors.initials: FJ
authors.lastname: White
mesh_terms: D000818:Animals; D019256:Cadmium Chloride / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002712:Chlorides; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D002586:Cesium; D013779:Tetrodotoxin; D019789:Tetraethylammonium; C028019:cesium chloride; D007736:Kynurenic Acid; D003042:Cocaine; D009543:Nifedipine; D019256:Cadmium Chloride; D002118:Calcium