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Nature Medicine 9, 15 - 16 (2003)
doi:10.1038/nm0103-15

Unmet expectations: The brain minds

William A. Carlezon Jr.1 & Roy A. Wise2

  1. Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA
  2. Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, USA

Correspondence to: William A. Carlezon Jr.1 e-mail: carlezon@mclean.harvard.edu


Addiction research has become increasingly focused on how addictive drugs affect neural signaling within the brain's reward circuitry. New work shows that the frustration of not receiving drugs when they are expected can also affect the inner workings of reward circuits.


The past decade has brought major insights into how addictive drugs affect intracellular signaling in the brain circuitry that controls drug-seeking habits. At almost every level of neuronal function—second messenger cascades, gene expression, receptor and transporter trafficking, ion channel permeability, neuronal discharge rate, microtubule expression and dendrite sprouting— repeated drug experiences alter the reward system 1.

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