title: Exposure to cocaine regulates inhibitory synaptic transmission in the nucleus accumbens.
abstract: Medium spiny neurons (MSNs) within the nucleus accumbens shell (NAc) function to gate and prioritize emotional/motivational arousals for behavioral output. The neuronal output of NAc MSNs is mainly determined by the integration of membrane excitability and excitatory/inhibitory synaptic inputs. Whereas cocaine-induced alterations at excitatory synapses and membrane excitability have been extensively examined, the overall functional output of NAc MSNs following cocaine exposure is still poorly defined because little is known about whether inhibitory synaptic input to these neurons is affected by cocaine. Here, our results demonstrate multidimensional alterations at inhibitory synapses in NAc neurons following cocaine self-administration in rats. Specifically, the amplitude of miniature IPSCs (mIPSCs) was decreased after 21 d withdrawal from 5 d cocaine self-administration. Upon re-exposure to cocaine after 21 d withdrawal, whereas the amplitude of mIPSCs remained downregulated, the frequency became significantly higher. Furthermore, the reversal potential of IPSCs, which was not significantly altered during withdrawal, became more hyperpolarized upon cocaine re-exposure. Moreover, the relative weight of excitatory and inhibitory inputs to NAc MSNs was significantly decreased after 1 d cocaine withdrawal, increased after 21 d withdrawal, and returned to the basal level upon cocaine re-exposure after 21 d withdrawal. These results, together with previous results showing cocaine-induced adaptations at excitatory synapses and intrinsic membrane excitability of NAc MSNs, may provide a relatively thorough picture of the functional state of NAc MSNs following cocaine exposure.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Mami
authors.initials: M
authors.lastname: Otaka
authors.forename: Masago
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Brian R
authors.initials: BR
authors.lastname: Lee
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Neumann
authors.forename: Ranji
authors.initials: R
authors.lastname: Cui
authors.forename: Yanhua H
authors.initials: YH
authors.lastname: Huang
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013569:Synapses / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D013779:Tetrodotoxin; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D003042:Cocaine