Glutamate Receptors on Dopamine Neurons Control the Persistence of Cocaine Seeking
Autor: | Rafael Luján, Ainhoa Bilbao, Bénédicte Balland, Briac Halbout, Rolf Sprengel, Carles Sanchis-Segura, Christian Lüscher, Rainer Spanagel, Günther Schütz, Jan Rodriguez Parkitna, David Engblom, Lionel Dahan, Rosanna Parlato, Stephanie Perreau-Lenz, Manuel Mameli |
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Rok vydání: | 2008 |
Předmět: |
Patch-Clamp Techniques
Time Factors PROTEINS Neuroscience(all) Membrane Potentials/drug effects/genetics Receptors AMPA/deficiency HUMDISEASE Conditioning Operant/drug effects/physiology AMPA receptor Neurotransmission Mice sysneuro Receptors N-Methyl-D-Aspartate/deficiency Dopamine medicine Animals humdisease Mice Knockout Ventral Tegmental Area/cytology Gamma-Aminobutyric Acid/pharmacology Behavior Animal musculoskeletal neural and ocular physiology General Neuroscience Glutamate receptor Motor Activity/physiology Neurons/drug effects/ physiology Valine/analogs & derivatives/pharmacology proteins Conditioned place preference ddc:616.8 Excitatory Amino Acid Antagonists/pharmacology nervous system Synaptic plasticity Excitatory postsynaptic potential NMDA receptor Dopamine/ metabolism SYSNEURO Psychology Cocaine-Related Disorders/metabolism/ physiopathology Neuronal Plasticity/drug effects/genetics Neuroscience Receptors Glutamate/ physiology medicine.drug |
Zdroj: | Neuron, Vol. 59, No 3 (2008) pp. 497-508 Neuron |
ISSN: | 0896-6273 |
DOI: | 10.1016/j.neuron.2008.07.010 |
Popis: | SummaryCocaine strengthens excitatory synapses onto midbrain dopamine neurons through the synaptic delivery of GluR1-containing AMPA receptors. This cocaine-evoked plasticity depends on NMDA receptor activation, but its behavioral significance in the context of addiction remains elusive. Here, we generated mice lacking the GluR1, GluR2, or NR1 receptor subunits selectively in dopamine neurons. We report that in midbrain slices of cocaine-treated mice, synaptic transmission was no longer strengthened when GluR1 or NR1 was abolished, while in the respective mice the drug still induced normal conditioned place preference and locomotor sensitization. In contrast, extinction of drug-seeking behavior was absent in mice lacking GluR1, while in the NR1 mutant mice reinstatement was abolished. In conclusion, cocaine-evoked synaptic plasticity does not mediate concurrent short-term behavioral effects of the drug but may initiate adaptive changes eventually leading to the persistence of drug-seeking behavior. |
Databáze: | OpenAIRE |
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