• DOI:10.1126/science.1187801
• Corpus ID: 32191373

Transition to Addiction Is Associated with a Persistent Impairment in Synaptic Plasticity

@article{Kasanetz2010TransitionTA,
  title={Transition to Addiction Is Associated with a Persistent Impairment in Synaptic Plasticity},
  author={Fernando Kasanetz and V{\'e}ronique Deroche-Gamonet and Nad{\`e}ge Berson and {\'E}ric Balado and Mathieu Lafourcade and Olivier J.J. Manzoni and Pier Vincenzo Piazza},
  journal={Science},
  year={2010},
  volume={328},
  pages={1709 - 1712}
}

• F. Kasanetz, V. Deroche-Gamonet, +4 authors P. Piazza
• Published 25 June 2010
• Psychology, Biology
• Science

Addicts Lose Plasticity What are the biological mechanisms associated with the transition from occasional drug use to addiction? In rats, like in humans, even after a prolonged period of drug intake, only a limited number of animals develop addiction-like behavior despite the amount of drug taken by all subjects being the same. Kasanetz et al. (p. 1709) compared the expression of N-methyl-d-aspartate (NMDA)–dependent long-term depression (NMDA-LTD) in the nucleus accumbens of addicted and nonaddicted rats. Initially, once drug self-administration had been learned and consolidated, but before the appearance of addiction-like behavior, LTD was suppressed in all animals independently of their vulnerability to addiction at a later stage. However, after 2 months, when addiction-like behavior appears, LTD was persistently lost in the addicted animals. In contrast, normal NMDA-LTD reappeared in animals that maintained a controlled drug intake without becoming addicted. Loss of glutamate receptor–dependent synaptic plasticity in the brain is associated with the transition to cocaine addiction. 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.