Addicts Lose Plasticity

Science Signaling  29 Jun 2010:
Vol. 3, Issue 128, pp. ec201
DOI: 10.1126/scisignal.3128ec201

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. 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.

F. Kasanetz, V. Deroche-Gamonet, N. Berson, E. Balado, M. Lafourcade, O. Manzoni, P. V. Piazza, Transition to addiction is associated with a persistent impairment in synaptic plasticity. Science 328, 1709–1712 (2010). [Abstract] [Full Text]