title: Transition to addiction is associated with a persistent impairment in synaptic plasticity.
abstract: Chronic exposure to drugs of abuse induces countless modifications in brain physiology. However, the neurobiological adaptations specifically associated with the transition to addiction are unknown. Cocaine self-administration rapidly suppresses long-term depression (LTD), an important form of synaptic plasticity in the nucleus accumbens. Using a rat model of addiction, we found that animals that progressively develop the behavioral hallmarks of addiction have permanently impaired LTD, whereas LTD is progressively recovered in nonaddicted rats maintaining a controlled drug intake. By making drug seeking consistently resistant to modulation by environmental contingencies and consequently more and more inflexible, a persistently impaired LTD could mediate the transition to addiction.
authors.affiliation: INSERM U862, NeuroCentre Magendie, 147 Rue Léo Saignat, 33077, Bordeaux Cedex, France.
authors.forename: Fernando
authors.initials: F
authors.lastname: Kasanetz
authors.forename: Véronique
authors.initials: V
authors.lastname: Deroche-Gamonet
authors.forename: Nadège
authors.initials: N
authors.lastname: Berson
authors.forename: Eric
authors.initials: E
authors.lastname: Balado
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lafourcade
authors.forename: Olivier
authors.initials: O
authors.lastname: Manzoni
authors.forename: Pier Vincenzo
authors.initials: PV
authors.lastname: Piazza
mesh_terms: D000818:Animals; D016739:Behavior, Addictive; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D036881:Long-Term Synaptic Depression; D009714:Nucleus Accumbens / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012646:Self Administration; D009435:Synaptic Transmission
chemical_list: D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D018698:Glutamic Acid; D003042:Cocaine