title: Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization.
abstract: Cocaine-induced alterations in synaptic glutamate function in nucleus accumbens are thought to mediate drug-related behaviors such as psychomotor sensitization. However, previous studies have examined global alterations in randomly selected accumbens neurons regardless of their activation state during cocaine-induced behavior. We recently found that a minority of strongly activated Fos-expressing accumbens neurons are necessary for cocaine-induced psychomotor sensitization, whereas the majority of accumbens neurons are less directly involved. We assessed synaptic alterations in these strongly activated accumbens neurons in Fos-GFP mice, which express a fusion protein of Fos and GFP in strongly activated neurons, and compared these alterations with those in surrounding non-activated neurons. Cocaine sensitization produced higher levels of 'silent synapses', which contained functional NMDA receptors and nonfunctional AMPA receptors only in GFP-positive neurons, 6-11 d after sensitization. Thus, distinct synaptic alterations are induced in the most strongly activated accumbens neurons that mediate psychomotor sensitization.
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, US National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland, USA.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Koya
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Cruz
authors.forename: Robert
authors.initials: R
authors.lastname: Ator
authors.forename: Sam A
authors.initials: SA
authors.lastname: Golden
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Hoffman
authors.forename: Carl R
authors.initials: CR
authors.lastname: Lupica
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Hope
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001703:Biophysics; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology*; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D015763:2-Amino-5-phosphonovalerate; D003042:Cocaine