Getting to the Bottom of Drug Cravings

Science's STKE  29 Nov 2005:
Vol. 2005, Issue 312, pp. tw428
DOI: 10.1126/stke.3122005tw428

Behavioral sensitization, an animal model for drug craving, involves neural adaptations in the mesocorticolimbic regions of the brain, including the nucleus accumbens. Synaptic plasticity in the nucleus accumbens, especially long-term depression (LTD), plays an important role in behavioral sensitization. Using new synthetic peptide inhibitors, Brebner et al. showed that LTD in nucleus accumbens is mediated by clathrin-dependent regulated endocytosis of AMPA receptors. An AMPA-specific inhibitor delivered to neurons in the nuclear accumbens blocked behavioral sensitization. Thus, LTD in the nuclear accumbens is mediated by facilitated endocytosis of postsynaptic AMPA receptors and may be involved in the pathogenesis of drug craving.

K. Brebner, T. P. Wong, L. Liu, Y. Liu, P. Campsall, S. Gray, L. Phelps, A. G. Phillips, Y. T. Wang, Nucleus accumbens long-term depression and the expression of behavioral sensitization. Science 310, 1340-1343 (2005). [Abstract] [Full Text]