title: Repeated cocaine exposure increases fast-spiking interneuron excitability in the rat medial prefrontal cortex.
abstract: The medial prefrontal cortex plays a key role in cocaine addiction. However, how chronic cocaine exposure affects cortical networks remains unclear. Most studies have focused on layer 5 pyramidal neurons (the circuit output), while the response of local GABAergic interneurons to cocaine remains poorly understood. Here, we recorded from fast-spiking interneurons (FS-IN) after repeated cocaine exposure and found altered membrane excitability. After cocaine withdrawal, FS-IN showed an increase in the number of spikes evoked by positive current injection, increased input resistance, and decreased hyperpolarization-activated current. We also observed a reduction in miniature excitatory postsynaptic currents, whereas miniature inhibitory postsynaptic current activity was unaffected. We show that, in animals with cocaine history, dopamine receptor D(2) activation is less effective in increasing FS-IN intrinsic excitability. Interestingly, these alterations are only observed 1 wk or more after the last cocaine exposure. This suggests that the dampening of D(2)-receptor-mediated response may be a compensatory mechanism to rein down the excitability of FS-IN.
authors.affiliation: Molecular Neurophysiology and Biophysics Section, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-3715, USA. campanacea@mail.nih.gov
authors.forename: Emilie
authors.initials: E
authors.lastname: Campanac
authors.forename: Dax A
authors.initials: DA
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D055369:Miniature Postsynaptic Potentials; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013997:Time Factors
chemical_list: D017448:Receptors, Dopamine D2; D003042:Cocaine
keywords: cocaine addiction; interneurons; intrinsic excitability; medial prefrontal cortex