title: Cocaine-induced plasticity in the nucleus accumbens is cell specific and develops without prolonged withdrawal.
abstract: Cocaine induces plasticity at glutamatergic synapses in the nucleus accumbens (NAc). Withdrawal was suggested to play an important role in the development of this plasticity by studies showing that some changes only appear several weeks after the final cocaine exposure. In this study, the requirement for prolonged withdrawal was evaluated by comparing the changes in glutamatergic transmission induced by two different noncontingent cocaine treatments: a short treatment followed by prolonged withdrawal, and a longer treatment without prolonged withdrawal. Recordings were performed from mouse medium spiny neurons (MSNs) in the NAc at the same time after the first cocaine injection under both treatments. A similar increase in the frequency of glutamate-mediated miniature EPSCs was observed in D(1)-expressing MSNs after both cocaine treatments, demonstrating that prolonged withdrawal was not required. Furthermore, larger AMPA receptor-to-NMDA receptor ratios, higher spine density, and enlarged spine heads were observed in the absence of withdrawal after a long cocaine treatment. These synaptic adaptations expressed in D(1)-containing MSNs of the NAc core were not further enhanced by protracted withdrawal. In conclusion, a few repeated cocaine injections are enough to trigger adaptations at glutamatergic synapses in D(1)-expressing MSNs, which, although they take time to develop, do not require prolonged cocaine withdrawal.
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Dobi
authors.forename: Gail K
authors.initials: GK
authors.lastname: Seabold
authors.forename: Christine H
authors.initials: CH
authors.lastname: Christensen
authors.forename: Roland
authors.initials: R
authors.lastname: Bock
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007274:Injections, Intraperitoneal; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009483:Neuropsychological Tests; D009714:Nucleus Accumbens / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D011897:Random Allocation; D018091:Receptors, AMPA / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013997:Time Factors
chemical_list: D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D003042:Cocaine