Transition to addiction is associated with a persistent impairment in synaptic plasticity.
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.
Kasanetz
Fernando
F
INSERM U862, NeuroCentre Magendie, 147 Rue Léo Saignat, 33077, Bordeaux Cedex, France.
Deroche-Gamonet
Véronique
V
Berson
Nadège
N
Balado
Eric
E
Lafourcade
Mathieu
M
Manzoni
Olivier
O
Piazza
Pier Vincenzo
PV
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
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