1. ¹Departments of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
2. ²Department of Psychiatry, Philadelphia VA Medical Center, University of Pennsylvania, Philadelphia, PA, USA

Correspondence: Dr P Kalivas, Departments of Neurosciences, Medical University of South Carolina, 173 Ashley Ave, BSB 410, Charleston, SC 29425, USA. Tel: +1 843 792 4400; Fax: +1 843 792 4423; E-mail: kalivasp@musc.edu

Received 12 July 2007; Revised 8 August 2007; Accepted 8 August 2007; Published online 5 September 2007.

Abstract

Using addictive drugs can evolve from controlled social use into the compulsive relapsing disorder that characterizes addiction. This transition to addiction results from genetic, developmental, and sociological vulnerabilities, combined with pharmacologically induced plasticity in brain circuitry that strengthens learned drug-associated behaviors at the expense of adaptive responding for natural rewards. Advances over the last decade have identified the brain circuits most vulnerable to drug-induced changes, as well as many associated molecular and morphological underpinnings. This growing knowledge has contributed to an expanded understanding of how drugs usurp normal learning circuitry to create the pathology of addiction, as evidenced by involuntary activation of reward circuits in response to drug-associated cues and simultaneous reports of drug craving. This new understanding provides unprecedented potential opportunities for novel pharmacotherapeutic targets in treating addiction. There appears to be plasticity associated with the addiction phenomenon in general as well as changes produced by addiction to a specific class of addicting drugs. These findings also provide the basis for the current understanding of addiction as a chronic, relapsing disease of the brain with changes that persist long after the last use of the drug. Here, we describe the neuroplasticity in brain circuits and cell function induced by addictive drugs that is thought to underlie the compulsions to resume drug-taking, and discuss how this knowledge is impelling exploration and testing of novel addiction therapies.