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

Fernando Kasanetz,^1,2,* Véronique Deroche-Gamonet,^1,2,* Nadège Berson,^1,2 Eric Balado,^1,2 Mathieu Lafourcade,^1,2 Olivier Manzoni,^1,2,, Pier Vincenzo Piazza^1,2,,

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.

¹ INSERM U862, NeuroCentre Magendie, 147 Rue Léo Saignat, 33077, Bordeaux Cedex, France.
² Université de Bordeaux, 147 Rue Léo Saignat, 33077, Bordeaux Cedex, France.

These authors contributed equally to this work.

To whom correspondence should be addressed. E-mail: olivier.manzoni{at}inserm.fr (O.M.); pier-vincenzo.piazza{at}inserm.fr (P.V.P.)

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