Drug Addiction: The Yin and Yang of Hedonic Homeostasis

abused in humans increases the reward value of ICSS, Department of Neuropharmacology and drug withdrawal decreases the reward value of ICSS The Scripps Research Institute (reviewed by Koob et al., 1993). The increases in reward La Jolla, California 92037 threshold or decreases in reward have been observed following the withdrawal of opiates, stimulants, and al-Drug addiction is usually defined as compulsion to take cohol and appear to be dose related in that the more a drug with loss of control over drug intake. The term drug that is administered over time, the larger the with-substance dependence is used to describe a syndrome drawal response. basically equivalent to addiction and the diagnostic cri-If a deficit reward state defines addiction, it could teria used describe symptoms that lead to loss of control be produced by several mechanisms. First, genetic or in drug intake. Substance use, substance abuse, and environmental factors could produce some neurobio-substance dependence are separate, definable entities logical deficit that requires reversal, perhaps by drug in most formulations. An important challenge for neuro-initiation. Alternatively, chronic drug taking itself could biological research is to understand how the transition produce a form of deficit state that required self-medica-occurs between controlled drug use and the loss of tion to reverse. This type of deficit state could be hypoth-control that defines addiction or substance dependence esized to exist at the molecular, cellular, and system and what molecular, cellular, and system processes level, and the minireviews in this issue discuss numerous contribute to the development of drug dependence. A neuropharmacological mechanisms for such perturba-neuroadaptive view of drug dependence was originally tions. based on the phenomenon of tolerance and withdrawal, However, drug dependence not only involves acquisi-adaptive processes that have been hypothesized to be tion of drug taking and maintenance of drug taking, the body's attempt to counter the acute effects of the but also functions as a chronic relapsing disorder with drug. Such adaptations have been explored at all levels reinstatement of drug taking after detoxification and ab-of drug dependence research from the behavioral to the stinence. Both the positive and negative affective states molecular (reviewed by Koob and Bloom, 1988). More can become associated with stimuli in the drug-taking recently, another adaptive process, the phenomenon environment or even internal cues through classical con-of sensitization, has been conceptualized as a critical ditioning processes (Wikler, 1973). Reexposure to these neuroadaptive process (Robinson and Berridge, 1993). conditioned …