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
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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