Neuroscience of Addiction

occur with the transition from occasional drug use to pathological abuse and addiction are only partially un-La Jolla, California 92037 derstood as yet. To reach a more complete understanding , these events will have to be integrated with the animal models of the different elements of the addiction Human addictions are chronically relapsing disorders process, including models of the transition from simple characterized by compulsive drug taking, an inability drug taking to compulsive use at the molecular, cellular, to limit the intake of drugs, and the emergence of a and behavioral levels. In this review, we will focus in withdrawal syndrome during cessation of drug taking particular on the factors that drive drug-seeking behav-(dependence). The development of an addiction impacts ior at different stages of the addiction cycle (Koob and on several separate neurobiological processes, and Le Moal, 1997), and we will place particular emphasis these effects are both drug-and drug use–dependent. on trying to identify what is currently known and what In animal models of addiction, changes in specific neu-remains to be elucidated. rotransmitter systems within a highly limited band of structures, including specific parts of the nucleus ac-cumbens and amygdala, may underlie drug reward and Neurobiological Substrates for the Acute the motivational effects associated with dependence. Reinforcing Effects of Drugs of Abuse Changes in the signals mediated by several neurotrans-Animals and humans will readily self-administer the mitters, including dopamine, opioid peptides, and corti-same classes of drugs, and such self-administration cotropin-releasing factor (CRF), and in the regulation of defines these drugs as positive reinforcers (Headlee et selected transcription factors within the neurons of this al., 1955). The powerful reinforcing properties of such reward circuit, may underlie the vulnerability to relapse drugs are revealed by the efforts experimental animals that characterizes addiction in humans. will perform to get them, such as pressing a lever multiple times to receive an intravenous injection of the drug. While early work focused on drug-taking behaviors in Animal Models of Addiction dependent animals (largely primates), subsequent stud-Addiction, also known as substance dependence (Amer-ies have replicated the same behaviors in nondepen-ican Psychiatric Association, 1994), is a chronically re-dent animals (largely rodents) (Schuster and Thompson, lapsing disorder that is characterized by three major 1969). Since rodents are more tractable experimentally, elements: (1) compulsion to seek and take the drug, (2) they have provided much recent insight into the perti-loss of control in limiting intake, and (3) emergence …